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CHEMISTRY (619 journals)                  1 2 3 4 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 14)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 27)
ACS Catalysis     Hybrid Journal   (Followers: 44)
ACS Chemical Neuroscience     Hybrid Journal   (Followers: 22)
ACS Combinatorial Science     Hybrid Journal   (Followers: 23)
ACS Macro Letters     Hybrid Journal   (Followers: 26)
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 41)
ACS Nano     Hybrid Journal   (Followers: 296)
ACS Photonics     Hybrid Journal   (Followers: 14)
ACS Symposium Series     Full-text available via subscription  
ACS Synthetic Biology     Hybrid Journal   (Followers: 25)
Acta Chemica Iasi     Open Access   (Followers: 5)
Acta Chimica Slovaca     Open Access   (Followers: 2)
Acta Chimica Slovenica     Open Access   (Followers: 1)
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7)
Acta Scientifica Naturalis     Open Access   (Followers: 3)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Adsorption Science & Technology     Open Access   (Followers: 6)
Advanced Functional Materials     Hybrid Journal   (Followers: 60)
Advanced Science Focus     Free   (Followers: 5)
Advances in Chemical Engineering and Science     Open Access   (Followers: 69)
Advances in Chemical Science     Open Access   (Followers: 18)
Advances in Chemistry     Open Access   (Followers: 22)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19)
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Advances in Environmental Chemistry     Open Access   (Followers: 7)
Advances in Enzyme Research     Open Access   (Followers: 10)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
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Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 12)
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Advances in Nanoparticles     Open Access   (Followers: 15)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Polymer Science     Hybrid Journal   (Followers: 45)
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Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 3)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 8)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Al-Kimia : Jurnal Penelitian Sains Kimia     Open Access  
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 68)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 21)
American Journal of Chemistry     Open Access   (Followers: 31)
American Journal of Plant Physiology     Open Access   (Followers: 11)
American Mineralogist     Hybrid Journal   (Followers: 15)
Analyst     Full-text available via subscription   (Followers: 39)
Angewandte Chemie     Hybrid Journal   (Followers: 171)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 253)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 5)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 9)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 13)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 2)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 9)
Applied Spectroscopy     Full-text available via subscription   (Followers: 24)
Applied Surface Science     Hybrid Journal   (Followers: 32)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 2)
Asian Journal of Chemistry and Pharmaceutical Sciences     Open Access  
Atomization and Sprays     Full-text available via subscription   (Followers: 4)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access  
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Hybrid Journal   (Followers: 367)
Biochemistry Insights     Open Access   (Followers: 6)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 10)
Bioinspired Materials     Open Access   (Followers: 5)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 2)
Biomacromolecules     Hybrid Journal   (Followers: 22)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 7)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 5)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 133)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 87)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 1)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 6)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 70)
Catalysis for Sustainable Energy     Open Access   (Followers: 8)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 7)
Catalysis Science and Technology     Free   (Followers: 8)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 10)
Cellulose     Hybrid Journal   (Followers: 7)
Cereal Chemistry     Full-text available via subscription   (Followers: 4)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 22)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 74)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 27)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
Chemical Reviews     Hybrid Journal   (Followers: 197)
Chemical Science     Open Access   (Followers: 26)
Chemical Technology     Open Access   (Followers: 28)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 57)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 24)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 7)
Chemistry & Biology     Full-text available via subscription   (Followers: 32)
Chemistry & Industry     Hybrid Journal   (Followers: 7)
Chemistry - A European Journal     Hybrid Journal   (Followers: 159)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 16)
Chemistry and Materials Research     Open Access   (Followers: 21)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Open Access   (Followers: 3)
Chemistry Letters     Full-text available via subscription   (Followers: 44)
Chemistry of Materials     Hybrid Journal   (Followers: 264)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 20)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 1)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 4)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 12)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 11)
Chromatographia     Hybrid Journal   (Followers: 24)
Chromatography     Open Access   (Followers: 2)
Chromatography Research International     Open Access   (Followers: 6)
Cogent Chemistry     Open Access   (Followers: 2)
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 11)
Colloids and Interfaces     Open Access  
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 6)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
Combustion Science and Technology     Hybrid Journal   (Followers: 22)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Communications Chemistry     Open Access  
Composite Interfaces     Hybrid Journal   (Followers: 7)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 1)
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Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 4)
Copernican Letters     Open Access   (Followers: 1)
Corrosion Series     Full-text available via subscription   (Followers: 6)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 6)
Croatica Chemica Acta     Open Access  
Crystal Structure Theory and Applications     Open Access   (Followers: 4)
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Current Catalysis     Hybrid Journal   (Followers: 2)
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Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
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Current Science     Open Access   (Followers: 71)
Current Trends in Biotechnology and Chemical Research     Open Access   (Followers: 3)
Dalton Transactions     Full-text available via subscription   (Followers: 23)
Detection     Open Access   (Followers: 3)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  

        1 2 3 4 | Last

Journal Cover
Bioorganic Chemistry
Journal Prestige (SJR): 0.85
Citation Impact (citeScore): 4
Number of Followers: 10  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0045-2068 - ISSN (Online) 1090-2120
Published by Elsevier Homepage  [3162 journals]
  • Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory
           activity, and in silico study of S-naproxen derivatives
    • Abstract: Publication date: March 2019Source: Bioorganic Chemistry, Volume 83Author(s): Ghulam Mohiuddin, Khalid Mohammed Khan, Uzma Salar, Kanwal, Muhammad Arif Lodhi, Abdul Wadood, Muhammad Riaz, Shahnaz Perveen Current study is based on the biology-oriented drug synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2–39 including hydrazide 1, Schiff bases 2–21, aroyl substituted hydrazides 22–24, sulfohydrazides 25–34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36–39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1–39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC50 = 14.01 ± 0.23–76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme.Graphical abstractGraphical abstract for this article
  • New iridal-type triterpenoid derivatives with cytotoxic activities from
           Belamcanda chinensis
    • Abstract: Publication date: March 2019Source: Bioorganic Chemistry, Volume 83Author(s): Jiayuan Li, Gang Ni, Li Li, Yanfei Liu, Zhenpeng Mai, Renzhong Wang, Dequan Yu Eight new iridal-type triterpenoid derivatives, including two noriridals with ether bridge (1–2); two iridals lactone (3–4), four monocyclic iridals (5–8), together with five known iridals (9–14) were identified from the rhizome of Belamcanda chinensis. Their structures were elucidated on the basis of comprehensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Bioassay results showed that belamcanoxide B (1) exhibited moderated cytotoxic activities against HCT-116 and MCF-7 cell lines with IC50 values of 5.58 and 3.35 μM.Graphical abstractGraphical abstract for this article
  • 2-Aryl-quinazolin-4(3H)-ones as an inhibitor of leishmania folate pathway:
           In vitro biological evaluation, mechanism studies and molecular docking
    • Abstract: Publication date: Available online 17 October 2018Source: Bioorganic ChemistryAuthor(s): Angel H. Romero, Noris Rodríguez, Henry Oviedo To identify new agents for the American Cutaneous Leishmaniasis treatment, a series of 2-aryl-quinazolin-4(3H)-ones were tested against L. mexicana, L. braziliensis and L. amazonensis parasites as potential inhibitor of folic metabolism pathway. In general, the L.braziliensis and L.mexicana promastigote parasites were more sensitive to the action of the quinazolinones than L. amazonensis. The most active derivatives showed low-micromolar EC50 ranging from 4 to 10 μM, being 1.3 to 4 fold more potent than glucantime reference drug. A complete in vitro evaluation on intracellular amastigote, axenic amastigote and murine peritoneal macrophage were performed for the most active derivatives. The compounds 2j, 2h, 2t and 2u displayed acceptable responses against intracellular amastigote compared to reference drug, excellent antileishmanial activities against axenic amastigote (LD50 ranging from 1 to 4 μM) and relative low toxicities on peritoneal macrophages. To validate the efficacy of these four derivatives, an in vitro evaluation was performed against an antimony-resistant amastigote strain; identifying to 2h and 2u as promising antileishmanial leads for further pharmacokinetics and in vivo studies. Experimental mechanism assays putted in evidences that the most active compounds act as folate inhibitor. A tentative molecular docking on pteridine reductase 1 (PTR1) enzyme showed that the most active quinazolinones 2j and 2t are located in almost identical place compared with methotrexate reference into active site.Graphical abstractGraphical abstract for this article
  • α-Pyrones, secondary metabolites from fungus Cephalotrichum microsporum
           and their bioactivities
    • Abstract: Publication date: Available online 17 October 2018Source: Bioorganic ChemistryAuthor(s): He Zhu, Dawei Li, Qingsong Yan, Yue An, Xiaokui Huo, Tianyuan Zhang, Mengyue Zhang, Chao Wang, Mingyu Xia, Xiaochi Ma, Yixuan Zhang Cephalotrichum microsporum (SYP-F 7763) was a fungus isolated from the rhizosphere soil of traditional Chinese medicine Panax notoginseng. The EtOAc extract of Cephalotrichum microsporum cultivated on sterilized moistened-rice medium was separated by various chromatographic techniques, which yielded 11 metabolites (1–11) of this fungus. On the basis of the widely spectroscopic data, the chemical structures of isolated metabolites were determined, most of which were α-pyrones, including 5 compounds (4–7, and 10) unreported. In the anti-bacterial bioassay, compound 1 displayed significant inhibitory effects on three pathogenic bacteria, MR S. aureus, S. aureus, and B. cereus. α-Pyrones 2, 3, and 5–7 also displayed moderate inhibitory effects on MR S. aureus, S. aureus, and B. subtilis, which could be the major anti-bacterial constituents of Cephalotrichum microsporum. Additionally, compounds 1, 4, and 5 displayed significant cytotoxicity on five human cancer cell lines, with the IC50 values < 20 μM, which are more effective than positive control 5-fluorouracil. Therefore, α-pyrones were important secondary metabolites of Cephalotrichum microsporum, which displayed anti-bacterial and anti-tumor activities.Graphical abstractGraphical abstract for this article
  • Preparation, characterization and in vitro activity of a
           docetaxel–albumin conjugate
    • Abstract: Publication date: Available online 17 October 2018Source: Bioorganic ChemistryAuthor(s): Jing Gao, Shougang Jiang, Xuewei Zhang, Yujie Fu, Zhiguo Liu Docetaxel is one of the most effective anticancer drugs. However, the current formulation of docetaxel contains Tween 80 and ethanol as the solvent, which can cause severe side effects. Consequently, the development of new type of formulation of docetaxel with high efficiency and low side effects is a very important issue. In this study, we explored the covalent linking of docetaxel and albumin via one organic linker. 6-Maleimidocaproic acid was applied to link the C2’ hydroxyl group of docetaxel with the cysteine-34 of albumin to obtain 1:1 docetaxel–albumin conjugate. The synthesized conjugate can control the release of docetaxel in the bovine serum. Furthermore, in vitro cell cytotoxicity experiments indicated that the docetaxel–albumin conjugate have high activities for human prostate cancer cell line PC3 and human breast cancer cell line MCF-7. The present study provides a valuable strategy for further development of a new type of docetaxel–albumin prodrug.Graphical abstractGraphical abstract for this article
  • Synthesis and Evaluation of an AZD2461 [18F]PET Probe in Non-Human
           Primates Reveals the PARP-1 Inhibitor to be Non-Blood-Brain Barrier
    • Abstract: Publication date: Available online 17 October 2018Source: Bioorganic ChemistryAuthor(s): Sean W. Reilly, Laura N. Puentes, Alexander Schmitz, Chia-Ju Hsieh, Chi-Chi Weng, Catherine Hou, Shihong Li, Yin-Ming Kuo, Prashanth Padakanti, Hsiaoju Lee, Aladdin A. Riad, Mehran Makvandi, Robert H. Mach Poly(ADP-ribose)polymerase-1 inhibitor (PARPi) AZD2461 was designed to be a weak P-glycoprotein (P-gp) analogue of FDA approved olaparib. With this chemical property in mind, we utilized the AZD2461 ligand architecture to develop a CNS penetrant and PARP-1 selective imaging probe, in order to investigate PARP-1 mediated neuroinflammation and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Our work led to the identification of several high-affinity PARPi, including AZD2461 congener 9e (PARP-1 IC50 = 3.9±1.2 nM), which was further evaluated as a potential 18F-PET brain imaging probe. However, despite the similar molecular scaffolds of 9e and AZD2461, our studies revealed non-appreciable brain-uptake of [18F]9e in non-human primates, suggesting AZD2461 to be non-CNS penetrant.Graphical abstractGraphical abstract for this article
  • A novel bi-functional chalcone inhibits multi-drug resistant
           Staphylococcus aureus and potentiates the activity of fluoroquinolones
    • Abstract: Publication date: Available online 17 October 2018Source: Bioorganic ChemistryAuthor(s): Vivek Kumar Gupta, Rashmi Gaur, Atin Sharma, Jawed Akther, Mahak Saini, Rajendra Singh Bhakuni, Ranjana Pathania Staphylococcus aureus is the leading cause of bacteraemia and the dwindling supply of effective antibacterials has exacerbated the problem of managing infections caused by this bacterium. Isoliquiritigenin (ISL) is a plant flavonoid that displays therapeutic potential against S. aureus. The present study identified a novel mannich base derivatives of ISL, IMRG4, active against Vancomycin intermediate S. aureus (VISA). IMRG4 damages the bacterial membranes causing membrane depolarization and permeabilization, as determined by loss of salt tolerance, flow cytometric analysis, propidium idodie and fluorescent vancomycin uptake. It reduces the intracellular invasion of HEK-293 cells by S. aureus and decreases the staphylococcal load in different organs of infected mice models. In addition to anti-staphylococcal activity, IMRG4 inhibits the multidrug efflux pump, NorA, which was determined by molecular docking and EtBr efflux assays. In combination, IMRG4 significantly reduces the MIC of norfloxacin for clinical strains of S. aureus including VISA. Development of resistance against IMRG4 alone and in combination with norfloxacin was low and IMRG4 prolongs the post-antibiotic effect of norfloxacin. These virtues combined with the low toxicity of IMRG4, assessed by MTT assay and haemolysis, makes it an ideal candidate to enter drug development pipeline against S. aureus.Graphical abstractGraphical abstract for this article
  • Synthesis, in vitro urease inhibition and molecular docking studies of
           some novel quinazolin-4(3H)-one derivatives containing triazole,
           thiadiazole and thiosemicarbazide functionalities
    • Abstract: Publication date: Available online 16 October 2018Source: Bioorganic ChemistryAuthor(s): Emre Menteşe, Gülay Akyüz, Mustafa Emirik, Nimet Baltaş A new series of quinazolinone derivatives containing triazole, thiadiazole, thiosemicarbazide functionalities was synthesized and then screened for their in vitro urease inhibition properties. Most of the compounds showed excellent activity with IC50 values ranging between 1.88±0.17 and 6.42±0.23 µg/mL, compared to that of thiourea (IC50 = 15.06±0.68) and acetohydroxamic acid (IC50 = 21.03±0.94), as reference inhibitors. Among the synthesized molecules, compounds 5c, 5e and 5a showed the best inhibitory effect against urease enzyme with IC50 values of 1.88±0.17µM, 1.90±0.10 and 1.96±0.07 µg/mL, respectively. Moreover in order to give better understanding of the inhibitory activity of synthesized compounds, molecular docking studies were applied at the target sites of jack bean urease enzyme (JBU). Their binding poses and energy calculations were analyzed using induced fit docking (IFD) and prime-MMGBSA tool. Binding poses of studied compounds were determined using induced fit docking (IFD) algorithms.Graphical abstractGraphical abstract for this article
  • bioNMR-based identification of natural anti-Aβ compounds in
           Peucedanum ostruthium
    • Abstract: Publication date: Available online 12 October 2018Source: Bioorganic ChemistryAuthor(s): Alessandro Palmioli, Sara Bertuzzi, Ada De Luigi, Laura Colombo, Barbara La Ferla, Mario Salmona, Ivano De Noni, Cristina Airoldi The growing interest in medicinal plants for the identification of new bioactive compounds and the formulation of new nutraceuticals and drugs prompted us to develop a powerful experimental approach allowing the detailed metabolic profiling of complex plant extracts, the identification of ligands of macromolecular targets of biomedical relevance and a preliminary characterization of their biological activity. To this end, we selected Peucedanum ostruthium, a plant traditionally employed in Austria and Italy for its several potential therapeutic applications, as case study. We combined the use of NMR and UPLC-HR-MS for the identification of the metabolites present in its leaves and rhizome extracts. Due to the significant content of polyphenols, particularly chlorogenic acids, recently identified as anti-amyloidogenic compounds, polyphenols-enriched fractions were prepared and tested for their ability to prevent Aβ1-42 peptide aggregation and neurotoxicity in a neuronal human cell line. STD-NMR experiments allowed the detailed identification of Aβ oligomers’ ligands responsible for the anti-amyloidogenic activity. These data provide experimental protocols and structural information suitable for the development of innovative molecular tools for prevention, therapy and diagnosis of AD.Graphical abstractGraphical abstract for this article
  • Synthesis of novel N-(1,3-thiazol-2-yl)benzamide clubbed oxadiazole
           scaffolds: Urease inhibition, Lipinski rule and molecular docking analyses
    • Abstract: Publication date: Available online 12 October 2018Source: Bioorganic ChemistryAuthor(s): Muhammad Athar Abbasi, Hussain Raza, Aziz-ur-Rehman, Sabahat Zahra Siddiqui, Syed Adnan Ali Shah, Mubashir Hassan, Sung-Yum Seo Present work aimed to synthesize some unique bi-heterocyclic benzamides as lead compounds for the in vitro inhibition of urease enzyme, followed by in silico studies. These targeted benzamides were synthesized in good yields through a multi-step protocol and their structures were confirmed by IR, 1H-NMR, 13C-NMR, EI-MS and elemental analysis. The in vitro screening results showed that most of the ligands exhibited good inhibitory potentials against the urease. Chemo-informatics analysis envisaged that all these compounds obeyed the Lipinski's rule. Molecular docking results showed that 7h exhibited good binding energy value (-8.40 kcal/mol) and was bound within the active region of urease enzyme. From the present investigation, it was inferred that some of these potent urease inhibitors might serve as novel templates in drug designing.Graphical abstractGraphical abstract for this article
  • Design, synthesis, structural characterization and in vitro evaluation of
           new 1,4-disubstituted-1,2,3-triazole derivatives against glioblastoma
    • Abstract: Publication date: Available online 11 October 2018Source: Bioorganic ChemistryAuthor(s): Veronica D. da Silva, Bruna M. de Faria, Eduardo Colombo, Lucas Ascari, Gabriella P.A. Freitas, Leonã S. Flores, Yraima Cordeiro, Luciana Romão, Camilla D. Buarque A new series of 1,4-disubstituted-1,2,3-triazole derivatives were synthesized through the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (Click chemistry) and their inhibitory activities were evaluated against different human glioblastoma (GBM) cell lines, including highly drug-resistant human cell lines GBM02, GBM95. The most effective compounds were 9d, containing the methylenoxy moiety linked to triazole and the tosyl-hydrazone group, and the symmetrical bis-triazole 10a, also containing methylenoxy moiety linked to triazole. Single crystal X-ray diffraction analysis was employed for structural elucidation of compound 9d. In silico analyses of physicochemical, pharmacokinetic, and toxicological properties suggest that compounds 8a, 8b, 8c, 9d, and 10a are potential candidates for central nervous system-acting drugs.Graphical abstractGraphical abstract for this article
  • Design and synthesis of novel quinazolinone-1,2,3-triazole hybrids as new
           anti-diabetic agents: in vitro α-glucosidase inhibition, kinetic, and
           docking study
    • Abstract: Publication date: Available online 11 October 2018Source: Bioorganic ChemistryAuthor(s): Mina Saeedi, Maryam Mohammadi-Khanaposhtani, Parvaneh Pourrabia, Nima Razzaghi, Reza Ghadimi, Somaye Imanparast, Mohammad Ali Faramarzi, Fatemeh Bandarian, Ensieh Nasli Esfahani, Maliheh Safavi, Hossein Rastegar, Bagher Larijani, Mohammad Mahdavi, Tahmineh Akbarzadeh A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity leading to efficient anti-diabetic agents. All synthesized compounds exhibited good inhibitory activity against yeast α-glucosidase (IC50 values in the range of 181.0-474.5 µM) even much more potent than standard drug acarbose (IC50 = 750.0). Among them, quinazolinone-1,2,3-triazoles possessing 4-bromobenzyl moiety connected to 1,2,3-triazole ring (10g and 10p) demonstrated the most potent inhibitory activity towards α-glucosidase. Compound 10g inhibited α-glucosidase in a competitive manner with Ki value of 117 µM. Furthermore, the binding modes of the most potent compounds 10g and 10p in the α-glucosidase active site was studied through in silico docking studies. Also, lack of cytotoxicity of compounds 10g and 10p was confirmed via MTT assay.Graphical abstractA novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity and all them exhibited α-glucosidase inhibitory activity more than standard drug acarbose.Graphical abstract for this article
  • Antibacterial activity against drug-resistant microbial pathogens of
           cytochalasan alkaloids from the arthropod-associated fungus Chaetomium
           globosum TW1-1
    • Abstract: Publication date: Available online 10 October 2018Source: Bioorganic ChemistryAuthor(s): Weixi Gao, Yan He, Fengli Li, Chenwei Chai, Jinwen Zhang, Jieru Guo, Chunmei Chen, Jianping Wang, Hucheng Zhu, Zhengxi Hu, Yonghui Zhang By feeding 1-methyl-l-tryptophan (1-MT) into cultures of the arthropod-associated fungus Chaetomium globosum TW1-1, three novel cytochalasan alkaloids, termed as armochaetoglosins A–C (1–3), together with five known analogues, namely prochaetoglobosin I (4), chaetoglobosin T (5), chaetoglobosin C (6), armochaetoglobin Y (7), and chaetoglobosin Vb (8), were isolated and characterized. Their structures including absolute configurations were elucidated by means of NMR spectroscopy, single-crystal X-ray crystallography, and comparison of the experimental electronic circular dichroism (ECD) spectra. Structurally, compounds 1–3 represented the first examples of 1'-N-methyl-chaetoglobosins, which were possibly biosynthesized from the additive 1-MT rather than tryptophan. Additionally, compound 3 showed the highest antibacterial activity against K. pneumoniae and ESBL-E. coli with MIC values of 4.0 μg/mL and 16.0 μg/mL, respectively, wherein the inhibitory effect of 3 against K. pneumoniae was stronger than that of the clinically used antibiotic meropenem, with an MIC value of 8 μg/mL. Our findings may provide new chemical templates for the development of new antibacterial agents against drug-resistant microbial pathogens.Graphical abstractGraphical abstract for this article
  • Dual effects of isoflavonoids from Pueraria lobata roots on estrogenic
           activity and anti-proliferation of MCF-7 human breast carcinoma cells
    • Abstract: Publication date: Available online 10 October 2018Source: Bioorganic ChemistryAuthor(s): Soo-Yeon Ahn, Mun Seok Jo, Dahae Lee, Seon-Eun Baek, Jiwon Baek, Jae Sik Yu, Jeyun Jo, Hwayoung Yun, Ki Sung Kang, Jeong-Eun Yoo, Ki Hyun Kim Pueraria lobata root (PLR), well known as Kudzu root, has recently become commercially available in Western dietary supplements for menopausal symptoms. The scientific basis for its action has been attributed to the action of phytoestrogens. This study aimed to investigate the estrogen-like activity of isoflavonoids isolated from P. lobata root and their safety with respect to their effect on breast cancer cell proliferation. In an E-screen assay, crude MeOH extract of PLR significantly increased the proliferation of MCF-7 cells in a concentration-dependent manner. Among the four fractions obtained by solvent fractionation of MeOH extract, the n-BuOH fraction had significant estrogen-like activities at all concentrations tested. Phytochemical analysis of the n-BuOH fraction led to the isolation of 10 isoflavones (1-10), among which genistein (10) had significant estrogen-like activities at all concentrations tested. These activities were significantly enhanced by treatment with genistein and 17β-estradiol compared with 17β-estradiol alone, and this effect was mediated by decreased expression of estrogen receptor (ER)α and phospho-ERα in MCF-7 cells. In a cell cytotoxicity assay, genistein (10) exhibited significant cytotoxicity in both ER-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. This cytotoxicity was characterized by the induction of apoptotic cells stained with annexin V conjugated with Alexa Fluor 488 and involved activation of mitochondria-independent and -dependent apoptosis pathways in MCF-7 cells. Our results demonstrated that genistein (10) has estrogen-like effects dependent on ER pathway activation and anti-proliferative effects mediated by the apoptosis pathway rather than the ER pathway in MCF-7 breast cancer cells.Graphical abstractGraphical abstract for this article
  • Design, Synthesis and molecular modeling study of certain VEGFR-2
           Inhibitors based on Thienopyrimidne Scaffold as Cancer Targeting Agents
    • Abstract: Publication date: Available online 10 October 2018Source: Bioorganic ChemistryAuthor(s): Amna Ghith, Khairia M. Youssef, Nasser S. M. Ismail, Khaled A. M. Abouzid Different series of novel thieno [2,3-d]pyrimidine derivative (9a-d,10a-f,l,m and 15a-m) were designed, synthesized and evaluated for their ability to in vitro inhibit VEGFR-2 enzyme. Also, the cytotoxicity of the final compounds was tested against a panel of 60 different human cancer cell lines by NCI. The VEGFR-2 enzyme inhibitory results revealed that compounds 10d, 15d and 15g are among the most active inhibitors with IC50 values of 2.5, 5.48 and 2.27 µM respectively, while compound 10a remarkably showed the highest cell growth inhibition with mean growth inhibition (GI) percent of 31.57% .It exhibited broad spectrum anti-proliferative activity against several NCI cell lines specifically on human breast cancer (T7-47D) and renal cancer (A498) cell lines of 85.5% and 77.65% inhibition respectively. To investigate the mechanistic aspects underlying the activity, further biological studies like flow cytometry cell cycle together with caspase-3 colorimetric assays were carried on compound 10a. Flow cytometric analysis on both MCV-7 and PC-3 cancer cells revealed that it induced cell-cycle arrest in the G0-G1phase and reinforced apoptosis via activation of caspase-3. Furthermore, molecular modeling studies have been carried out to gain further understanding of the binding mode in the active site of VEGFR-2 enzyme and predict pharmacokinetic properties of all the synthesized inhibitors.Graphical abstractGraphical abstract for this article
  • Synthesis, Characterization, Crystal Structure of the Coordination Polymer
           Zn(II) with Thiosemicarbazone of Glyoxalic Acid and Their Inhibitory
           Properties Against Some Metabolic Enzymes
    • Abstract: Publication date: Available online 10 October 2018Source: Bioorganic ChemistryAuthor(s): Mansura Huseynova, Ajdar Medjidov, Parham Taslimi, Mahizar Aliyeva A new coordination polymer Zn(II) with thiosemicarbazone glyoxalic acid H2GAT was obtained in this study. According to the X-ray diffraction data, the coordination of the Zn(II) ion is carried out by one sulfur atom, in the thiol form , one nitrogen atom of the azomethine group and two oxygen atoms of the carboxylate groups, one of which belongs to neighbouring complex molecule . The oxygen atom of the water molecule completes Zn(II) ion environment to a distorted square-pyramidal structure. The binding of the monomer complex into polimer occurs through the bridge oxygen atom of carboxylate group. This complex is effective inhibitor of the α-glycosidase, butyrylcholinesterase (BChE), cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase enzymes (AChE) enzymes with Ki values of 1.45±0.23 µM for hCA I, 2.04±0.11 µM for hCA II, 3.47±0.88 µM for α-glycosidase,0.47±0.10 µM for BChE, and 0.58±0.13 µM for AChE, respectively.Graphical abstractThis compound can be important to the treatment of diabetic and AD complications.Graphical abstract for this article
  • Synthesis of new pyrazoles and pyrozolo [3,4-b] pyridines as
           anti-inflammatory agents by inhibition of COX-2 enzyme
    • Abstract: Publication date: Available online 10 October 2018Source: Bioorganic ChemistryAuthor(s): Lamia W. Mohamed, Mohamed A. Shaaban, Ashraf F. Zaher, Shimaa M. Alhamaky, Ayman M. Elsahar New pyrazoles and pyrazolo[3,4-b] pyridines were synthesized and their structure was confirmed by elemental analyses as well as IR, 1H NMR, 13C NMR, and mass spectral data. All the newly synthesized derivatives were evaluated in vitro for inhibitory activity against COX-1 and COX-2 enzymes and their IC50 values were calculated, most of the derivatives showed good inhibitory activity with derivatives IVb, IVh and IVJ showing inhibitory activity better than celecoxib. Moreover, the eight most potent derivatives IVa, IVb, IVc, IVd, IVe, IVh, IVJ, and IVL were selected for in vivo assay to measure their effect on paw edema in rates and their ulcerogenic effect. Compounds IVa, IVb and IVc were found to be the most active and selective as COX-2 inhibitors and most effective in protection from edema, they were also found to have lowest ulcerogenic effect among all derivatives.Graphical abstractGraphical abstract for this article
  • Pyranopyrazoles as efficient antimicrobial agents: Green, one pot and
           multicomponent approach
    • Abstract: Publication date: Available online 25 September 2018Source: Bioorganic ChemistryAuthor(s): Guda Mallikarjuna Reddy, Jarem Raul Garcia, Grigory V. Zyryanov Innovative therapeutic heterocycles having precisely thiadiazolyl-pyranopyrazole fragments were prepared by using the ecofriendly synthetic route. Entire compounds formed in quantitative yields. All the composites tested for their antimicrobial effectiveness against four microbial, two beneficial fungi’s and accurately measured the minimum inhibitory concentrations (MIC and MBC/MFC), along with some initial structure activity relationships (SARs) also discussed. From the biological outcomes, the motif 6f provided an outstanding activity against all six pathogens. The possible presence of a nitro substituent on this composite may undoubtedly enhance the activity. In addition, amalgams 6d, 6g and 6l displayed promising antimicrobial results. This may be justified to the presence of electron capture group attached to the benzene ring, while the combinations 6j and 6k were zero effect towards all bacterial strains. The other compounds are excellent to low antimicrobial efficiency. The intriguing point was observed that all the active compounds had in common immense antibacterial effectiveness on Gram-negative bacteria than Gram-positive one and more antifungal activity on A. niger compare to other fungus. All things considered and suggested that this outstanding green synthetic approach is used to develop biological active compounds. On top of that, biological results confirmed that these biologically energetic motifs suitable for additional preclinical examine with the aim of standing novel innovative drugs.Graphical abstractGraphical abstract for this article
  • α-Sulfonamidophosphonates as New Anti-Mycobacterial Chemotypes: Design,
           Development of Synthetic Methodology, and Biological Evaluation
    • Abstract: Publication date: Available online 19 September 2018Source: Bioorganic ChemistryAuthor(s): Srikant Bhagat, Metheku Supriya, Satish Pathak, Dharmarajan Sriram, Asit K. Chakraborti Tuberculosis (TB) is the leading cause of death worldwide due to bacterial infection. The scarcity of effective drugs to treat the disease and the compounded problems due to the development of resistance to the available therapeutics and TB-HIV synergism drive medicinal chemists to search for new anti-Mtb chemotypes. Towards this endeavor, the α-sulfonamidophosphonate moiety has been identified as new anti-Mtb chemotype through the scaffold hopping as the design strategy, development of an effective synthetic methodology using green chemistry tools, and evaluation of anti-TB activity of the synthesized compounds against Mtb (Mycobacterium tuberculosis) H37Rv. Out of the sixteen compounds, five have been found to have MIC values of 1.56 μg/mL and one 3.125 μg/mL. The five most active compounds are non-cytotoxic to RAW 264.7 (mouse leukemic monocyte macrophage) cell lines. The compounds are found to possess acceptable values of the various parameters for drug likeness in accordance with the Lipinski rule with the topological surface area (tPSA) of> 70 that suggest eligibility of these new molecular entities for further consideration as potential drug candidates.Graphical abstractThe α-sulfonamidophosphonates have been identified as new non-toxic anti-Mtb chemotypes with low micromolar MIC values and favourable drug like properties.Graphical abstract for this article
  • Antimicrobial and Antibiofilm Activity of Polyurethane/Hypericum
           perforatum Extract (PHPE) Composite
    • Abstract: Publication date: Available online 11 August 2018Source: Bioorganic ChemistryAuthor(s): O. Nazlı, T. Baygar, Ç.E. Demirci Dönmez, Ö. Dere, A.İ. Uysal, A. Aksözek, C. Işık, S. Akturk Microbial accumulation in materials used in sectors such as medical, textile and food can lead to serious diseases, infections and uncontrollable problems. Many of the materials used in the above-mentioned industries have highly sensitive surfaces for microorganisms and cause colonization and biofilm formation. Colonization and biofilm formation threaten human health and they cause many diseases that result in death every year. Antimicrobial materials have an important role in combating pathogens. This article is about a new material with antibiofilm and antimicrobial properties combining polyurethane and Hypericum perforatum extract (PHPE) together. Antimicrobial effect of H. perforatum extract was determined against three clinical pathogens; C. albicans, E. coli and S. aureus. The highest antimicrobial activity of H. perforatum extract was found against S. aureus strain. Antibiofilm analysis results revealed that H. perforatum was also inhibited by the biofilm formation of S. aureus by 56.85%. The combination of polyurethane material and H. perforatum extract (PHPE) resulted in 92.85% decrease in S. aureus biofilm compared to control group. The reduction of S. aureus after H. perforatum incorporation was revealed by Scanning Electron Microscopy (SEM) study. The results show that the polyurethane material combined with H. perforatum extract inhibits the formation of S. aureus biofilm.Graphical abstractGraphical abstract for this article
  • Novel quinazolin-4-one derivatives as potentiating agents of doxorubicin
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Monika Pospisilova, Martin Andrs, Martina Seifrtova, Radim Havelek, Daniel Jun, Pavel Tomsik, Lukas Prchal, Rafael Dolezal, Ales Tichy, Tomas Kucera, Jan Korabecny, Martina Rezacova We report the design, synthesis and biological evaluation of 17 novel 8-aryl-2-morpholino-3,4-dihydroquinazoline derivatives based on the standard model of DNA-PK and PI3K inhibitors. Novel compounds are sub-divided into two series where the second series of five derivatives was designed to have a better solubility profile over the first one. A combination of in vitro and in silico techniques suggested a plausible synergistic effect with doxorubicin of the most potent compound 14d on cell proliferation via DNA-PK and poly(ADP-ribose) polymerase-1 (PARP-1) inhibition, while alone having a negligible effect on cell proliferation.Graphical abstractGraphical abstract for this article
  • Hydrogen sulfide releasing enmein-type diterpenoid derivatives as
           apoptosis inducers through mitochondria-related pathways
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Fanxing Xu, Xiang Gao, Haonan Li, Shengtao Xu, Xu Li, Xu Hu, Zhanlin Li, Jinyi Xu, Huiming Hua, Dahong Li In this study, we combined two enemin-type diterpenoid derivatives with two well-established hydrogen sulfide moieties via ester or different anhydride linkers, to search apoptosis inducing drug candidate capable of hydrogen sulfide generating. Therefore, a series of hybrids were synthesized and superior antiproliferative efficacy accompanied with enhanced selectivity was observed under extensive pharmacological evaluations. A standard methylene blue (MB+) method was applied to measure the capacity for the hydrogen sulfide generation of all the target derivatives. One particular molecule A1, which contained α-thioctic acid moiety for hydrogen sulfide donating, manifested more potent antiproliferative activity. It exerted inhibitory effects against Bel-7402, SGC-7901 and A549 cell lines with IC50 values of 2.16, 5.07 and 6.98 μM respectively. While it exacted relatively low effects over human normal cell lines L-02 and PBMC with IC50 values of 15.81 μM for the prior and 14.15 μM for the latter, and displayed better selectivity index (SI) than parent diterpenoids. A high dosage of H2S release was also recorded. Hence, A1 was most suitable for mechanistic exploration on account of both safety and efficacy. The ensuing biological assays revealed central role of apoptosis in A1’s mode of action for antiproliferative efficacy, which led to further confirmation of G1 phase cell cycle arrest, mitochondria membrane potential collapse and apoptotic activation in Bel-7402 cells. Further western blot assay on intrinsic mitochondria pathway unlocked intricate interplay among a series of apoptotic related proteins in which Bax, caspase-3 and cytochrome c went through up-regulation, while Bcl-2, Bcl-xL and procaspase-3 undergone down-regulation. In a nutshell, a hydrogen sulfide releasing hybrid A1 was synthesized and antiproliferative evaluation identified it to be a worthy drug candidate for future in depth study.Graphical abstractGraphical abstract for this article
  • α-Tocopherol-ascorbic acid hybrid antioxidant based cationic amphiphile
           for gene delivery: Design, synthesis and transfection
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Venkanna Muripiti, Lohchania Brijesh, Hari Krishnareddy Rachamalla, Srujan Kumar Marepally, Rajkumar Banerjee, Srilakshmi V. Patri Natural antioxidants and vitamins have potential to protect biological systems from peroxidative damage induced by peroxyl radicals, α-tocopherol (Vitamin E, lipid soluble) and ascorbic acid (vitamin C, water soluble), well known natural antioxidant molecules. In the present study we described the synthesis and biological evaluation of hybrid of these two natural antioxidants with each other via ammonium di-ethylether linker, Toc-As in gene delivery. Two control cationic lipids N14-As and Toc-NOH are designed in such a way that one is with ascorbic acid moiety and no tocopherol moiety; another is with tocopherol moiety and no ascorbic acid moiety respectively. All the three cationic lipids can form self-assembled aggregates. The antioxidant efficiencies of the three lipids were compared with free ascorbic acid. The cationic lipids (Toc-As, N14-As and Toc-NOH) were formulated individually with a well-known fusogenic co-lipid DOPE and characterization studies such as DNA binding, heparin displacement, size, charge, circular dichroism were performed. The biological characterization studies such as cell viability assay and in vitro transfection studies were carried out with the above formulations in HepG2, Neuro-2a, CHO andHEK-293T cell lines. The three formulations showed their transfection efficiencies with highest in Toc-As, moderate inN14-As and least in Toc-NOH. Interestingly, the transfection efficiency observed with the antioxidant based conjugated lipid Toc-As is found to be approximately two and half fold higher than the commercially available lipofectamine 2000 at 4:1 charge ratio in Hep G2 cell lines. In the other cell lines studied the efficiency of Toc-As is found to be either higher or similarly active compared to lipofectamine 2000. The physicochemical characterization results show that Toc-As lipid is showing maximum antioxidant potency, strong binding with pDNA, least size and optimal zeta potential. It is also found to be least toxic in all the cell lines studied especially in Neuro-2a cell lines when compared to other two lipids. In summary, the designed antioxidant lipid can be exploited as a delivering system for treating ROS related diseases such as malignancy, brain stroke, etc.Graphical abstractGraphical abstract for this article
  • Six new compounds from the flowers of Chrysanthemum morifolium and their
           biological activities
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Peng-Fei Yang, Ya-Nan Yang, Zi-Ming Feng, Jian-Shuang Jiang, Pei-Cheng Zhang Flower of Chrysanthemum morifolium is widely used in China and Japan as a folk medicine in treatment of many diseases. However, its active compounds remain largely unknown. In the present work, we have isolated, purified and characterized six new compounds (1–6), including two new arylnaphthalene lignans and four new phenolic glycosides, together with eight known compounds (7–14), from the flower of C. morifolium. Their structures and absolute configurations were elucidated in detail using 1D and 2D NMR, UV, IR, ORD, HRESIMS and ECD spectrometric data. In addition, compounds 1–3 possessed the significant neuroprotective activity against hydrogen peroxide-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.Graphical abstractGraphical abstract for this article
  • Dioximes: Synthesis and biomedical applications
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Mohamed A. Motaleb, Adli A. Selim The selective properties of dioxime compounds were discovered and outlined in the beginning of 20th century by Tschugaeff [L.Z. Tschugaeff, Z. Anorg. Allgem. Chem. 46 (1905) 144]. Dioximes have special properties as analytical reagents for transition metals. Dioximes complexation properties with metals were carried out by many investigations and these complexations showed a wide range of applications such as antimicrobial and theranostic agents. This review will provide general synthetic methods of oximes especially dioximes and brief overview on the applications of dioximes (applications of their metal complexes).Graphical abstractGraphical abstract for this article
  • Novel Hybrids of Benzothiazole-1,3,4-oxadiazole-4-thiazolidinone:
           Synthesis, in silico ADME study, molecular docking and in vivo
           anti-diabetic assessment
    • Abstract: Publication date: Available online 13 October 2018Source: Bioorganic ChemistryAuthor(s): Rubina Bhutani, Dharam Pal Pathak, Garima Kapoor, Asif Husain, Md. Azhar Iqbal A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models. All the tested compounds demonstrated excellent to moderate reduction in blood glucose levels. Three of the compounds (Tz21, Tz7 and Tz10) showed excellent anti-diabetic effect by reducing concentration of glucose to 157.15±1.79 mg/dL, 154.39±1.71 mg/dL, 167.36±2.45 mg/dL, respectively better than the standard drug, pioglitazone, 178.32±1.88 mg/dL. Moreover, three derivatives Tz21, Tz4 and Tz24 with IC50 values of 0.21 ± 0.01 µM, 9.03 ± 0.12 µM and 11.96 ± 0.40 µM respectively also showed better inhibitory activities on alpha-glucosidase even more than the standard acarbose (IC50 = 18.5 ± 0.20 µM), indicating Tz21 has the highest inhibitory effect among the seven tested derivatives. Prediction of Drug like properties using molinspiration online software suggests that all the synthesized compounds have potential of becoming the orally active molecules. Thus, these novel hybrids could serve as potential candidates to become leads for the development of new drugs eliciting anti-hyperglycemic effect orally.Graphical abstractGraphical abstract for this article
  • Bioactive monoterpene indole alkaloids from Nauclea officinalis
    • Abstract: Publication date: Available online 13 October 2018Source: Bioorganic ChemistryAuthor(s): Yan-Ping Liu, Qing-Long Liu, Xiang-Lin Zhang, Hai-Yuan Niu, Chun-Yan Guan, Fu-Kang Sun, Wei Xu, Yan-Hui Fu Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3–8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1–8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of hydrocortisone. In addition, compounds 1–8 showed significant anti-HIV-1 activities with EC50 ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.Graphical abstractGraphical abstract for this article
  • Trichosanhemiketal A and B: two 13,14-seco-13,14-epoxyporiferastanes from
           the root of Trichosanthes kirilowii Maxim
    • Abstract: Publication date: Available online 13 October 2018Source: Bioorganic ChemistryAuthor(s): Manh Tuan Ha, Thanh Nam Phan, Jeong Ah Kim, Won Keun Oh, Jeong Hyung Lee, Mi Hee Woo, Byung Sun Min Of the 32 Trichosanthes species in China, T. kirilowii Maxim. is the most renowned species used in traditional Chinese medicine and has diverse pharmacological properties. However, most of the phytochemical studies of T. kirilowii have focused on the fruits and seeds. In our investigation of the chemical constituents of T. kirilowii roots, two previously undescribed sterols [trichosanhemiketal A and B (1 and 2)], together with 13 known compounds, were isolated and their structures were elucidated. To the best of our knowledge, this represents the first isolation of compounds with a 13,14-seco-13,14-epoxyporiferastane (1-2) skeleton from the Cucurbitaceae family. The anti-inflammatory activity of the isolated compounds was determined through an analysis of their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Of the compounds, 4, 5, 6, and 8 showed significant inhibitory activities, with IC50 values of 8.5, 15.1, 25.4, and 28.5 µM, respectively. In addition, compound 4 inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in a concentration-dependent manner.Graphical abstractGraphical abstract for this article
  • Synthesis and in vitro urease inhibitory activity of benzohydrazide
           derivatives, in silico and kinetic studies
    • Abstract: Publication date: Available online 10 October 2018Source: Bioorganic ChemistryAuthor(s): Azhar Abbas, Basharat Ali, Kanwal, Khalid Mohammed Khan, Jamshed Iqbal, Shafiq ur Rahman, Sumera Zaib, Shahnaz Perveen Benzohydrazide derivatives 1-43 were synthesized via “one-pot” reaction and structural characterization of these synthetic derivatives was carried out by different spectroscopic techniques such as 1H-NMR and EI-MS. The synthetic molecules were evaluated for their in vitro urease inhibitory activity. All synthetic derivatives showed good inhibitory activities in the range of (IC50 = 0.87 ± 0.31 - 19.0 ± 0.25 µM) as compared to the standard thiourea (IC50 = 21.25 ± 0.15 µM), except seven compounds 17, 18, 23, 24, 29, 30, and 41 which were found to be inactive. The most active compound of the series was compound 36 (IC50 = 0.87 ± 0.31 μM) having two chloro groups at meta positions of ring A and methoxy group at para position of ring B. The structure-activity relationship (SAR) of the active compounds was established on the basis of different substituents and their positions in the molecules. Kinetic studies of the active compounds revealed that compounds can inhibit enzyme via competitive and noncompetitive modes. In silico study was also performed to understand the binding interactions of the molecules (ligand) with the active site of enzyme.Graphical abstractGraphical abstract for this article
  • Design and Development of Novel p-Aminobenzoic Acid Derivatives as
           Potential Cholinesterase Inhibitors for the Treatment of Alzheimer’s
    • Abstract: Publication date: Available online 9 October 2018Source: Bioorganic ChemistryAuthor(s): Sushant K. Shrivastava, Saurabh K. Sinha, Pavan Srivastava, Prabhash N. Tripathi, Piyoosh Sharma, Manish K. Tripathi, Avanish Tripathi, Priyanka K. Choubey, Digambar K. Waiker, Lalit M. Aggarwal, Manish Dixit, Subhash C. Kheruka, Sanjay Gambhir, Sharmila Shankar, Rakesh K. Srivastava Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the ex vivo studies in the specific brain regions like the hippocampus, hypothalamus, and prefrontal cortex regions also exhibited AChE inhibition comparable to standard donepezil. The in silico molecular docking and dynamics simulations studies of the most potent compound 22 revealed the consensual interactions at the active site pocket of the AChE.Graphical abstractGraphical abstract for this article
  • Design, and facile synthesis of 1,3 diaryl-3-(arylamino)propan-1-one
           derivatives as the potential alpha-amylase inhibitors and antioxidants
    • Abstract: Publication date: Available online 9 October 2018Source: Bioorganic ChemistryAuthor(s): Roqia Bashary, Gopal L. Khatik Diabetes is the most prevalent metabolic disorder causing a high rate of mortality and morbidity. Recently alpha-amylase is reported to be good drug design target for the treatment of diabetes mellitus. We have designed 116 molecules based on aza-Michael adduct of trans-chalcone as 1,3 diaryl-3-(arylamino)propan-1-ones which were studied by molecular docking and among them best six derivatives were synthesized easily via aza-Michael addition on trans-chalcone using KOH as a catalyst and evaluated for alpha-amylase inhibition along with antioxidant activity. It was observed that all compounds have alpha-amylase inhibitory activity but at different extents. The molecule 3e is the most potent alpha-amylase inhibitor of this series. 3a is the second most potent compound, whereas only one molecule 3d has shown antioxidant activity.Graphical abstractGraphical abstract for this article
  • Design, synthesis and biological evaluation of novel ureido
           benzenesulfonamides incorporating 1,3,5-triazine moieties as potent
           carbonic anhydrase IX inhibitors
    • Abstract: Publication date: Available online 5 October 2018Source: Bioorganic ChemistryAuthor(s): Nabih Lolak, Suleyman Akocak, Silvia Bua, Claudiu T. Supuran A series of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties were obtained by reacting 4-isocyanato-benzenesulfonamide (2) with 2-amino-4,6-dicholoro-1,3,5-triazine (4). The 4-(3-(4,6-dichloro-1,3,5-triazin-2-yl)ureido) benzenesulfonamide (5) was subsequently derivatized by reaction with various nucleophiles such as, morpholine, ammonia, methyl amine, dimethyl amine, and piperidine. The ureido benzenesulfonamides incorporating triazinyl moieties were investigated as inhibitors of four selected physiologically relevant human carbonic anhydrase (hCA, EC isoforms, namely, hCA I, II, IX, and XII which are involved in various diseases such as glaucoma, epilepsy, obesity and cancer. The membrane-bound tumor-associated isoform hCA IX was potently inhibited with these compounds with Kis in the range of 0.91 to 126.2 nM. Specifically, compound 7j showed great potency against hCA IX with sub-nanomolar Ki of 0.91 nM. Since hCA IX is a validated drug target for anticancer agents, these isoform-selective and potent inhibitors may be considered of interest for further medicinal/pharmacologic studies.Graphical abstractGraphical abstract for this article
  • Design and synthesis of novel potent anticoagulant and anti-tyrosinase
           pyranopyrimidines and pyranotriazolopyrimidines: insights from molecular
           docking and SAR analysis
    • Abstract: Publication date: Available online 5 October 2018Source: Bioorganic ChemistryAuthor(s): Meriem Debbabi, Vijaykumar D Nimbarte, Samia Chekir, Sarra Chortani, Anis Romdhane, Hichem Ben jannet Pyrimidine-fused compounds are of great interest for the discovery of potent bioactive agents. This study describes the synthesis of novel pyranopyrimidines 3a-f and pyranotriazolopyrimidines 4a-d derivatives via the cyclocondensation reaction of α-functionalized iminoether 2, which was obtained from 2-amino-3-cyanopyrane 1, with a series of primary aromatic amines and hydrazides, respectively. Structures of all synthesized compounds were established on the basis of spectroscopic methods including 1H NMR, 13C NMR and ES-HRMS. They were finally tested for their anticoagulant and anti-tyrosinase activities. Significant results have been obtained and the structure-activity relationship (SAR) was discussed with the help of molecular docking analysis.Graphical abstractGraphical abstract for this article
  • 3-Aminobenzenesulfonamides incorporating acylthiourea moieties selectively
           inhibit the tumor-associated carbonic anhydrase isoform IX over the
           off-target isoforms I, II and IV
    • Abstract: Publication date: Available online 4 October 2018Source: Bioorganic ChemistryAuthor(s): Tanzeela Abdul Fattah, Silvia Bua, Aamer Saeed, Ghulam Shabir, Claudiu T. Supuran We describe the synthesis of a series of novel 1-aroyl/acyl-3-(3-aminosulfonylphenyl) thioureas (4a-k) acting as human carbonic anhydrase (hCA, EC inhibitors. Reaction of alkyl/aryl isothiocyanates with 3-aminobenzenesulfonamide afforded a series of the title compounds incorporating a variety of short as well as highly lipophilic long tails. The newly synthesized sulfonamides were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IV, and IX). Several compounds showed interesting inhibitory activity. The tumor-associated hCA IX was the most sensitive isoform to inhibition with these compounds, with KIs in the range of 21.5 – 44.0 nM and selectivity ratios over the major cytosolic isoform hCA II in the range of 3.35 – 37.3. The sulfonamides incorporating the phenylacetylthioureido and pentadecanoylthioureido moieties were the most hCA IX-selective inhibitors detected in this work, making them of interest for further investigations.Graphical abstractR = alkyl, aryl; KI (hCA IX) = 20-80 nMSelectivity ratio hCA IX/hCA II = 7.25 – 37.3Graphical abstract for this article
  • 1,2,4-Trisubstituted imidazolinones with dual carbonic anhydrase and p38
           mitogen-activated protein kinase inhibitory activity
    • Abstract: Publication date: Available online 1 October 2018Source: Bioorganic ChemistryAuthor(s): Hanan H. Georgey, Fatma M. Manhi, Walaa R. Mahmoud, Nehad A. Mohamed, Emanuela Berrino, Claudiu T. Supuran Various 1,2,4 trisubstituted imidazolin-5-one derivatives were synthesized and evaluated for their inhibitory activity against p38 mitogen-activated protein kinase (p38MAPK) and carbonic anhydrase (CA) enzymes aiming to explore potential dual inhibitors. Results revealed that compounds 3c, 3g, 3h, 4a, 6c and 6d were the most effective derivatives against p38αMAPK (IC50= 0.14, 0.14, 0.056, 0.14, 0.13 and 0.14 μM, respectively) compared to sorafenib (IC50= 1.58 μM) as standard drug. On the other hand, compound 4a revealed the best inhibitory activity against all the tested carbonic anhydrase isoforms CA I, II, IV and IX with Ki values of 95.0, 0.83, 6.90 and 12.4 nM, respectively compared to acetazolamide with Ki values 250, 12.1, 74 and 12.8 nM, respectively. Therefore, compound 4a can be considered as a potent dual p38αMAPK/CA inhibitor.Graphical abstractGraphical abstract for this article
  • Bioactivity-based analysis and chemical characterization of
           anti-inflammatory compounds from Curcuma zedoaria rhizomes using
           LPS-stimulated RAW264.7 cells
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Tae Kyoung Lee, Tuy An Trinh, Seoung Rak Lee, Sil Kim, Hae Min So, Eunjung Moon, Gwi Seo Hwang, Ki Sung Kang, Ji Hwan Kim, Noriko Yamabe, Ki Hyun Kim Inflammation is not only a self-defense response of the innate immune system, but also the pathogenesis mechanism of multiple diseases such as arthritis, neurodegeneration, and cancer. Curcuma zedoaria Roscoe (Zingiberaceae), an indigenous plant of India, has been used traditionally in Ayurveda and folk medicine. As part of our ongoing efforts to screen traditional medicinal plants exhibiting pharmacological potential and to characterize the compounds involved, we examined the anti-inflammatory effects of the MeOH extract of C. zedoaria rhizomes using lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells and found that MeOH extract inhibited the synthesis of nitric oxide (NO) in a dose-dependent manner (IC50: 23.44 ± 0.77 μg/mL). In our efforts to characterize the compounds responsible for these anti-inflammatory effects, bioactivity-guided fractionation of the MeOH extract and chemical investigation of its active hexane-soluble fraction led to the successful isolation of five sesquiterpenes (1–5), the structures of which were elucidated by NMR spectroscopic analysis and LC/MS analysis. Among them, curcuzedoalide (5) exhibited potent inhibitory effects on NO synthesis (IC50: 12.21 ± 1.67 μM) and also suppressed pre-inflammatory protein expression of iNOS and COX-2. Curcuzedoalide (5) was thus determined to be a contributor to the anti-inflammatory effect of C. zedoaria rhizomes and could be a potential candidate for therapeutic applications.Graphical abstractGraphical abstract for this article
  • How the surface functionalized nanoparticles affect conformation and
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Sathish Dyawanapelly, Pihu Mehrotra, Goutam Ghosh, Dhanashree D Jagtap, Prajakta Dandekar, Ratnesh Jain To understand the effect of counter ions (Na+) on the secondary conformation and functionality of the lysozyme, we have studied the interaction of lysozyme with counterion associated iron oxide nanoparticles (IONPs). The investigation was carried out at pH 7.4 and 9.0, with three different types of NPs, namely, bare IONPs, low molecular weight chitosan modified IONPs (LMWC-IONPs) and the counterion (Na+) associated sodium tripolyphosphate IONPs (STP-LMWC-IONPs) and confirmed by using various spectroscopy techniques. The difference in UV–vis absorbance (ΔA) between native and STP-LMWC-IONPs interacted hen egg white lysozyme (HEWL) was greater than that between native and NPs interacted HEWL at pH 9.0 compared with pH 7.4. Furthermore, STP-LMWC-IONPs exhibited quenching effect on lysozyme fluorescence spectrum at pH 9.0 due to binding of Na+ counterions to the protein, confirming denaturation of the latter. After HEWL interaction with STP-LMWC-IONPs (pH 9.0), CD spectra revealed a conformational change in the secondary structure of HEWL. Also, counterion induced lysozyme inactivation, due to interaction with nanoparticles at pH 9.0, was confirmed by enzymatic activity assay involving lysis of Micrococcus lysodeikticus. In conclusion, pH 9.0 was observed to be a more favorable condition, compared to pH 7.4, for the strongest electrostatic interaction between lysozyme and NPs. We postulate that the counterions in nanoparticle surface-coating can ameliorate protein misfolding or unfolding and also prevent their aggregation and, therefore, can be considered as a powerful and potential therapeutic strategy to treat incurable neurodegenerative disorders.Graphical abstractGraphical abstract for this article
  • Acridine-based (thio)semicarbazones and hydrazones: Synthesis, in vitro
           urease inhibition, molecular docking and in-silico ADME evaluation
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Ibanga Okon Isaac, Mariya al-Rashida, Shafiq Ur Rahman, Rima D. Alharthy, Asnuzilawati Asari, Abdul Hameed, Khalid Mohammed Khan, Jamshed Iqbal Urease is a bacterial enzyme that is responsible for virulence of various pathogenic bacteria such as Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumoniae, Ureaplasma urealyticum, Helicobacter pylori and Mycobacterium tuberculosis. Increased urease activity aids in survival and colonization of pathogenic bacteria causing several disorders especially gastric ulceration. Hence, urease inhibitors are used for treatment of such diseases. In search of new molecules with better urease inhibitory activity, herein we report a series of acridine derived (thio)semicarbazones (4a-4e, 6a-6l) that were found to be active against urease enzyme. Molecular docking studies were carried out to better comprehend the preferential mode of binding of these compounds against urease enzyme. Docking against urease from pathogenic bacterium S. pasteurii was also carried out with favorable results. In silico ADME evaluation was done to determine drug likeness of synthesized compounds.Graphical abstractGraphical abstract for this article
  • Unusual cadinane-type sesquiterpene glycosides with α-glucosidase
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Jun He, Jie-kun Xu, Xue-ge Pan, Xian-sheng Ye, Pin-yi Gao, Yu Yan, Chun-yang Xu, Gui-fen Qiang, Guan-hua Du, Yung-Chi Cheng, Wei-ku Zhang Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1–5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited marked α-glucosidase inhibitory activity except for 3in vitro.Graphical abstractGraphical abstract for this article
  • Bioactive staurosporine derivatives from the Streptomyces sp.
    • Abstract: Publication date: February 2019Source: Bioorganic Chemistry, Volume 82Author(s): Biao Zhou, Zhi-Juan Hu, Hao-Jian Zhang, Jia-Qi Li, Wan-Jing Ding, Zhong-Jun Ma Six new (1–6) and nine known (7–15) staurosporine derivatives were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. NB-A13. The structures of the new staurosporine derivatives were established by extensive spectroscopic data interpretation. The absolute configurations of 1 and 2 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. All of these compounds were screened for their cytotoxic activities against PC-3 and SW-620 cell lines. Compound 7 exhibited stronger inhibitory activity against SW-620 cell lines than the positive control staurosporine (25.10 nM), with IC50 values of 9.99 nM. Moreover, compounds 1–5, 8–13 and 15 also showed significant cytotoxicities with IC50 values ranging from 0.02 to 16.60 μM, while 6 exhibited no cytotoxic potency. Additionally, compounds 1–7 were also tested for enzyme inhibition activities of Protein kinase C theta (PKC-θ), and showed activity with IC50 values ranging from 0.06 to 9.43 μM except for compound 6, which has no inhibition activity.Graphical abstractSix new (1–6) and nine known (7–15) staurosporine derivatives were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. NB-A13. Compound 7 exhibited stronger inhibitory activity against SW-620 cell lines than the positive control staurosporine (25.10 nM), with IC50 values of 9.99 nM. Moreover, compounds 1–5, 8–13 and 15 also showed significant cytotoxicities with IC50 values ranging from 0.02 to 16.60 μM.Graphical abstract for this article
  • Design, synthesis and biological evaluation of
           N 1-(isoquinolin-5-yl)-N 2-phenylpyrrolidine-1,2-dicarboxamide derivatives
           as potent TRPV1 antagonists
    • Abstract: Publication date: Available online 25 September 2018Source: Bioorganic ChemistryAuthor(s): Mingxiang Gao, Cunbin Nie, Jinyu Li, Beibei Songm, Xinru Chengm, Erying Sun, Lin Yan, Hai Qian Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on a N1-(isoquinolin-5-yl)-N2-phenylpyrrolidine-1,2-dicarboxamide platform that evolved from a 5-aminoisoquinoline urea lead. Advancing the SAR of this series led to the eventual identification of 3b, comprising a p-Br substituted phenyl. In a TRPV1 functional assay, using cells expressing recombinant human TRPV1 channels, 3b displayed potent antagonism activated by capsaicin (IC50 = 0.084 μM) and protons (IC50 = 0.313 μM). In the preliminary analgesic and body temperature tests, 3b exhibited good efficacy in capsaicin-induced and heat-induced pain models and without hyperthermia side-effect. On the basis of its superior profiles, 3b could be considered as the lead candidate for the further development of antinociceptive drugs.Graphical abstractReported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on a N1-(isoquinolin-5-yl)-N2-phenylpyrrolidine-1,2-dicarboxamide platform that evolved from a 5-aminoisoquinoline urea lead.Graphical abstract for this article
  • Design, synthesis, modeling studies and biological evaluation of
           thiazolidine derivatives containing pyrazole core as potential
           anti-diabetic PPAR-γ agonists and anti-inflammatory COX-2 selective
    • Abstract: Publication date: Available online 25 September 2018Source: Bioorganic ChemistryAuthor(s): Khaled R.A. Abdellatif, Wael A.A. Fadaly, Gehan M. Kamel, Yaseen A.M.M. Elshaier, Mohammed A. El-Magd Nowadays, diabetes and its associated inflammatory complications are important public health problems worldwide. Market limitations of drugs with dual actions as anti-inflammatory (AI) and anti-diabetic have been led to a temptation for focusing on the discovery and development of new compounds with potential AI and anti-diabetic activities. Herein, we synthesized two new series containing pyrazole ring with vicinal diaryl rings as selective COX-2 moiety and thiazolidindione (series 12a-f) or thiazolidinone (series 13a-f) as anti-diabetic moiety and the two moieties were linked together with methylene or methylenehydrazone functionality. The two series were evaluated for their COX inhibition, AI activity and ulcerogenic liability and for the anti-diabetic activity; 12a-f and 13a-f were assessed in vitro against α-glucosidase, β- glucosidase, in vivo hypoglycemic activity (one day and 15 days studies) in addition to PPARγ activation study. Four compounds (12c, 12f, 13b and 13f) had higher COX-2 S.I. (8.69 – 9.26) than the COX-2 selective drug celecoxib (COX-2 S.I. = 8.60) and showed the highest AI activities and the lowest ulcerogenicity than other derivatives. Also, two thiazolidindione derivatives 12e and 12f and two thiazolidinone derivatives 13b and 13c showed higher inhibitory activities against α- and β-glucosidase (% inhibitory activity = 62.15, 55.30, 65.37, 59.08 for α-glucosidase and 57.42, 60.07, 58.19, 66.90 for β-glucosidase respectively) than reference compounds (acarbose with % inhibitory activity = 49.50 for α-glucosidase and D-saccharic acid 1,4-lactone monohydrate with % inhibitory activity = 53.42 for β-glucosidase) and also showed good PPAR-γ activation and good hypoglycemic effect in comparison to pioglitazone and rosiglitazone. Moreover, Shape comparison and docking studies were carried out to understand their interaction and similarity with standard drugs.Graphical abstractGraphical abstract for this article
  • The isolation, absolute configuration and activities of
           18(4→3)-abeo-abietane lactones from Tripterygium wilfordii
    • Abstract: Publication date: Available online 24 September 2018Source: Bioorganic ChemistryAuthor(s): Lin Ni, Li Li, Yingda Zang, Chuang-jun Li, Jie Ma, Tiantai Zhang, Dong-ming Zhang Phytochemical studies on the leaves of Tripterygium wilfordii led to the isolation of seven new 18(4→3)-abeo-abietane lactones, triptergulides E - K (1 - 7). The structure of the new compounds was elucidated on the basis of their spectroscopic analysis, and the absolute configurations of compounds were confirmed by ECD, calculated ECD, and X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Some compounds showed moderate inhibitory activities against NO, IL-6, and TNF-α production in LPS RAW 264.7 macrophage in vitro.Graphical abstractGraphical abstract for this article
  • Lead Compounds and Key Residues of Ribosomal Protein S1 in Drug-resistant
           Mycobacterium tuberculosis
    • Abstract: Publication date: Available online 21 September 2018Source: Bioorganic ChemistryAuthor(s): Yunbao Zhi, Yazhuang Dai, Juanjuan Yang, Shuhua Tan, Donghai Lin, Kejiang Lin Ribosomal protein S1 (RpsA) has been identified as a novel target of pyrazinoic acid (POA), which is the active form of pyrazinamide (PZA), in vivo. RpsA plays a crucial role in trans-translation, which is widespread in microbes. In our investigation, we first described the discovery of promising RpsA antagonists for drug-resistant mycobacterium (MtRpsAd438A) and M. smegmatis, as well as wild-type M. tuberculosis. These antagonists were discovered via structure/ligand-based virtual screening approaches. A total of 21 targeted compounds were selected by virtual screening, combined scores, affinity, similarities and rules for potential as drugs. Next, the affinities of these compounds for three targeted proteins were tested in vitro by applying various technologies, including fluorescence quenching titration (FQT), saturation transfer difference (STD), and chemical shift perturbation (CSP) assays. The results showed that seven compounds had a high affinity for the targeted proteins. Our discovery set the stage for discovering new chemical entities (NCEs) for PZA-resistant tuberculosis and providing key residues for rational drug design to target RpsA.Graphical abstractGraphical abstract for this article
  • Identification and Structure–Activity Relationship (SAR) of potent and
           selective oxadiazole-based agonists of Sphingosine-1-phosphate receptor
    • Abstract: Publication date: Available online 11 September 2018Source: Bioorganic ChemistryAuthor(s): Tianqi Liu, Jing Jin, Yonghui Chen, Qiumu Xi, Jinping Hu, Wenqiang Jia, Xiaoguang Chen, Yan Li, Xiaojian Wang, Dali Yin Agonism of S1P1 receptor has been proven to be responsible for peripheral blood lymphopenia and elicited the identification of various S1P1 modulators. In this paper we described a series of oxadiazole-based S1P1 direct-acting agonists disubstituted on terminal benzene ring, with high potency for S1P1 receptor and favorable selectivity against S1P3 receptor. In addition, two representative agents named 16-3b and 16-3g demonstrated impressive efficacy in lymphocyte reduction along with reduced effect on heart rate when orally administered. Furthermore, these compounds have been shown to possess desired pharmacokinetic (PK) and physicochemical profiles. The binding mode between 16-3b and the activated S1P1 model was also studied.Graphical abstractA series of oxadiazole-based S1P1 direct-acting agonists, with high affinity for S1P1 receptor and favorable selectivity against S1P3 receptor was deigned, synthesized and evaluated in vitro and vivo.Graphical abstract for this article
  • Pentamethinium Salts as Ligands for Cancer: Sulfated Polysaccharide
           Co-receptors as Possible Therapeutic Target
    • Abstract: Publication date: Available online 16 February 2018Source: Bioorganic ChemistryAuthor(s): Tomáš Bříza, Jarmila Králová, Silvie Rimpelová, Martin Havlík, Robert Kaplánek, Zdeněk Kejík, Pavel Martásek, Ivan Mikula, Petr Džubák, Marián Hajdúch, Tomáš Ruml, Vladimír Král A series of pentamethinium salts with benzothiazolium and indolium side units comprising one or two positive charges were designed and synthesized to determine the relationships among the molecular structure, charge density, affinity to sulfated polysaccharides, and biological activity. Firstly, it was found that the affinity of the pentamethinium salts to sulfated polysaccharides correlated with their biological activity. Secondly, the side heteroaromates displayed a strong effect on the cytotoxicity and selectivity towards cancer cells. Finally, doubly charged pentamethinium salts possessing benzothiazolium side units exhibited remarkably high efficacy against a taxol-resistant cancer cell line.Graphical abstractGraphical abstract for this article
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