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Medicinal Chemistry Research
Journal Prestige (SJR): 0.422  Citation Impact (citeScore): 2 Number of Followers: 12  Hybrid journal (It can contain Open Access articles)ISSN (Print) 1054-2523 - ISSN (Online) 1554-8120 Published by Springer-Verlag  [2626 journals]
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- NF-κB regulation by bisbenzylisoquinoline alkaloids in human T cells: a
structure–activity relationship study- Abstract: Suppressive potencies of tetrandrine, isotetrandrine, fangchinoline, berbamine, dauricine, cepharanthine, and armepavine on expression and activation of NF-κB in MOLT-4 cells, MOLT-4/DNR cells, peripheral blood mononuclear cells (PBMCs) of healthy subjects and PBMCs of dialysis patients were compared. In MOLT-4 cells, the suppressive potencies evaluated by the IC50 values were isotetrandrine > cepharanthine > tetrandrine > dauricine > fangchinoline > berbamine or armepavine. In MOLT-4/DNR cells, the order was isotetrandrine > tetrandrine > cepharanthine > fangchinoline > dauricine > berbamine or armepavine. In PBMCs of healthy subjects, the order was isotetrandrine > dauricine > fangchinoline > tetrandrine > cepharanthine > berbamine or armepavine. In PBMCs of dialysis patients, the order was isotetrandrine > fangchinoline > tetrandrine > cepharanthine > dauricine > berbamine or armepavine. Among them, isotetrandrine showed the strongest inhibitory effects on the expression of NF-κB and p-NF-κB in these cells. Accordingly, both 7- and 12-substitutions are suggested to influence the suppressive potency of bisbenzylisoquinoline alkaloids, though 7-substitution is likely to have less contribution. Bisbenzylisoquinoline alkaloid seems to be more suitable than monobenzylisoquinoline alkaloid to serve as a lead compound. Bisbenzylisoquinoline alkaloids with an 18-membered ring formed by two oxygen bridges seem to be superior to those with one oxygen. However, the binding sites of two oxygen bridges on the phenyl ring appear to have limited influence. These findings provide further insight into structure–activity relationships to the development of active analogs of this promising class of drugs for the treatment of diseases mediated by abnormalities of T cell activation.
PubDate: 2020-12-01
- Abstract: Suppressive potencies of tetrandrine, isotetrandrine, fangchinoline, berbamine, dauricine, cepharanthine, and armepavine on expression and activation of NF-κB in MOLT-4 cells, MOLT-4/DNR cells, peripheral blood mononuclear cells (PBMCs) of healthy subjects and PBMCs of dialysis patients were compared. In MOLT-4 cells, the suppressive potencies evaluated by the IC50 values were isotetrandrine > cepharanthine > tetrandrine > dauricine > fangchinoline > berbamine or armepavine. In MOLT-4/DNR cells, the order was isotetrandrine > tetrandrine > cepharanthine > fangchinoline > dauricine > berbamine or armepavine. In PBMCs of healthy subjects, the order was isotetrandrine > dauricine > fangchinoline > tetrandrine > cepharanthine > berbamine or armepavine. In PBMCs of dialysis patients, the order was isotetrandrine > fangchinoline > tetrandrine > cepharanthine > dauricine > berbamine or armepavine. Among them, isotetrandrine showed the strongest inhibitory effects on the expression of NF-κB and p-NF-κB in these cells. Accordingly, both 7- and 12-substitutions are suggested to influence the suppressive potency of bisbenzylisoquinoline alkaloids, though 7-substitution is likely to have less contribution. Bisbenzylisoquinoline alkaloid seems to be more suitable than monobenzylisoquinoline alkaloid to serve as a lead compound. Bisbenzylisoquinoline alkaloids with an 18-membered ring formed by two oxygen bridges seem to be superior to those with one oxygen. However, the binding sites of two oxygen bridges on the phenyl ring appear to have limited influence. These findings provide further insight into structure–activity relationships to the development of active analogs of this promising class of drugs for the treatment of diseases mediated by abnormalities of T cell activation.
- Triphenylphosphonium conjugates of 1,2,3-triazolyl nucleoside analogues.
Synthesis and cytotoxicity evaluation- Abstract: A series of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of several pyrimidine nucleosides was synthesized and evaluated for the in vitro cytotoxicity against human cancer cell lines M-HeLa, MCF-7, PANC-1, PC-3, DU145, SKOV-3, A275, and normal human cell line WI-38. In these TPP-conjugates triphenylphosphonium cation was attached via a tetramethylene chain to the N-3 atom of the heterocycle moiety (uracil, thymine, quinazoline-2,4-dione), which was coupled with the D-ribofuranosyl-1,2,3-triazol-4-yl fragment via methylene or tetramethylene linker. It was shown for the first time that the conjugation of 1,2,3-triazolyl derivatives of uridine, its analogues featuring quinazoline-2,4-dione fragment as well as uracil and thymine derivatives, having propargyl or a 1,2,3-triazolyl substituent at the N-1 atom, with a TPP-butyl cation endowed some of them with cytotoxic activity against human cancer cells. Among all human cancer cell lines used, DU-145 and A375 cells were the most sensitive to these TPP conjugates. At the same time, all tested compounds did not inhibit growth of normal cells WI-38. Propargyl containig TPP-conjugates of uracil 4f, 4j, and thymine 5f showed the highest cytotoxicity with IC50 values in the low micromolar concentration range. The present findings suggest that TPP-conjugates of uracil and thymine derivatives would be promising for further development as an anticancer agent.
PubDate: 2020-12-01
- Abstract: A series of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of several pyrimidine nucleosides was synthesized and evaluated for the in vitro cytotoxicity against human cancer cell lines M-HeLa, MCF-7, PANC-1, PC-3, DU145, SKOV-3, A275, and normal human cell line WI-38. In these TPP-conjugates triphenylphosphonium cation was attached via a tetramethylene chain to the N-3 atom of the heterocycle moiety (uracil, thymine, quinazoline-2,4-dione), which was coupled with the D-ribofuranosyl-1,2,3-triazol-4-yl fragment via methylene or tetramethylene linker. It was shown for the first time that the conjugation of 1,2,3-triazolyl derivatives of uridine, its analogues featuring quinazoline-2,4-dione fragment as well as uracil and thymine derivatives, having propargyl or a 1,2,3-triazolyl substituent at the N-1 atom, with a TPP-butyl cation endowed some of them with cytotoxic activity against human cancer cells. Among all human cancer cell lines used, DU-145 and A375 cells were the most sensitive to these TPP conjugates. At the same time, all tested compounds did not inhibit growth of normal cells WI-38. Propargyl containig TPP-conjugates of uracil 4f, 4j, and thymine 5f showed the highest cytotoxicity with IC50 values in the low micromolar concentration range. The present findings suggest that TPP-conjugates of uracil and thymine derivatives would be promising for further development as an anticancer agent.
- Functionalized imidazolium-based ionic liquids: biological activity
evaluation, toxicity screening, spectroscopic, and molecular docking
studies- Abstract: A series of long-chain imidazolium-based ionic liquids (ILs) 1-dodecyl-3-methylimidazolium chloride (1), 1,3-bis(octyloxycarbonylmethyl)imidazolium chloride (2) and 1-dodecyloxycarbonylmethyl-3-methyloxycarbonylmethylimidazolium chloride (3), were synthesized and evaluated as antimicrobials against a wide range of bacteria and fungi. Toxicological risks of selected compounds were assessed using the biomodels of various organizational and functional levels. All compounds demonstrated significant antibacterial and antifungal activity. The toxicity results indicate that ILs containing an ester functional group in the alkyl side chain exhibited much lower toxicity to D. magna and acetylcholinesterase inhibition than ILs with long alkyl chain without polar substituents, while toxicity toward Danio rerio was on a par. The HSA-binding properties of ILs have been investigated by FT-IR spectroscopy technique and the evidences have suggested that the test compounds could induce the protein unfolding and changes in the secondary structure of HSA. The docking studies were carried out to provide structural insights of the ILs–HSA-binding interactions. The docked compounds exhibit a high binding affinity to HSA and the hydrogen bonding, hydrophobic and electrostatic interactions played a major role in the process. ILs 2 and 3 may be perspective for further investigation as potential low-toxic biocides with high antimicrobial activity against reference and clinical multidrug-resistant strains.
PubDate: 2020-12-01
- Abstract: A series of long-chain imidazolium-based ionic liquids (ILs) 1-dodecyl-3-methylimidazolium chloride (1), 1,3-bis(octyloxycarbonylmethyl)imidazolium chloride (2) and 1-dodecyloxycarbonylmethyl-3-methyloxycarbonylmethylimidazolium chloride (3), were synthesized and evaluated as antimicrobials against a wide range of bacteria and fungi. Toxicological risks of selected compounds were assessed using the biomodels of various organizational and functional levels. All compounds demonstrated significant antibacterial and antifungal activity. The toxicity results indicate that ILs containing an ester functional group in the alkyl side chain exhibited much lower toxicity to D. magna and acetylcholinesterase inhibition than ILs with long alkyl chain without polar substituents, while toxicity toward Danio rerio was on a par. The HSA-binding properties of ILs have been investigated by FT-IR spectroscopy technique and the evidences have suggested that the test compounds could induce the protein unfolding and changes in the secondary structure of HSA. The docking studies were carried out to provide structural insights of the ILs–HSA-binding interactions. The docked compounds exhibit a high binding affinity to HSA and the hydrogen bonding, hydrophobic and electrostatic interactions played a major role in the process. ILs 2 and 3 may be perspective for further investigation as potential low-toxic biocides with high antimicrobial activity against reference and clinical multidrug-resistant strains.
- Antifungal activity of aminoalcohols and diamines against dermatophytes
and yeast- Abstract: Dermatomycoses are infections caused by fungi and yeasts and the drug treatment is considered expensive and extensive. Researchers are synthesizing new organic compounds in order to obtain more effective molecules that provide reduced adverse effects. Our research group has synthesized and evaluated the biological activities of aminoalcohol and diamine derivatives, which were considered active against human pathogenic fungi. Therefore, the objective of this study was to evaluate the in vitro antifungal activity of aminoalcohols and diamine derivatives against fungi and yeasts that cause dermatomycoses. The minimum inhibitory concentrations (MICs) and the minimum fungicidal concentration (MFC) of aminoalcohol (1–4) and diamine (5–13) derivatives was determined against Trichophyton mentagrophytes, T. rubrum, Epidermophyton floccosum, and Candida albicans according to protocols from the Clinical and Laboratory Standards Institute. All molecules exhibited fungicidal activity against the evaluated fungal strains, with the MIC and MFC ranging between 0.12 and 1000 μg/mL for filamentous fungi and 0.6 and 1250 μg/mL for yeasts. The best activity was attributed to diamines compared to aminoalcohols, with an emphasis on molecules 6 and 7. These results demonstrate the antifungal potential of the evaluated aminoalcohols and diamines against the four primary fungal species that cause dermatomycoses.
PubDate: 2020-12-01
- Abstract: Dermatomycoses are infections caused by fungi and yeasts and the drug treatment is considered expensive and extensive. Researchers are synthesizing new organic compounds in order to obtain more effective molecules that provide reduced adverse effects. Our research group has synthesized and evaluated the biological activities of aminoalcohol and diamine derivatives, which were considered active against human pathogenic fungi. Therefore, the objective of this study was to evaluate the in vitro antifungal activity of aminoalcohols and diamine derivatives against fungi and yeasts that cause dermatomycoses. The minimum inhibitory concentrations (MICs) and the minimum fungicidal concentration (MFC) of aminoalcohol (1–4) and diamine (5–13) derivatives was determined against Trichophyton mentagrophytes, T. rubrum, Epidermophyton floccosum, and Candida albicans according to protocols from the Clinical and Laboratory Standards Institute. All molecules exhibited fungicidal activity against the evaluated fungal strains, with the MIC and MFC ranging between 0.12 and 1000 μg/mL for filamentous fungi and 0.6 and 1250 μg/mL for yeasts. The best activity was attributed to diamines compared to aminoalcohols, with an emphasis on molecules 6 and 7. These results demonstrate the antifungal potential of the evaluated aminoalcohols and diamines against the four primary fungal species that cause dermatomycoses.
- Novel amide analogues of quinazoline carboxylate display selective
antiproliferative activity and potent EGFR inhibition- Abstract: In the present study, a novel series of quinazoline derivatives is developed for cancer therapy. All the synthesised analogues were evaluated against a panel of 60 human cancer cell lines for the antiproliferative activity. Significant and selective growth inhibition of several solid tumour cell lines such as NCI-H322M, NCI-H522 (non-small cell lung cancer), IGROV1, SK-OV-3 (ovarian cancer), TK-10 (renal cancer) and MDA-MB-468 (breast cancer) was observed. Further, all the new amide analogues strongly inhibited EGFR in low nanomolar range with morpholino quinazoline 10 producing activity (IC50 = 6.12 nM) comparable to standard drugs erlotinib and gefitinib. In addition, western blot analysis depicted inhibition of phosphorylation of EGFR by compounds 10 and 11 in MDA-MB-468 cells at 10 µM. Molecular docking studies showed the strong binding interactions with the active site of the EGFR protein. The current investigation could be extremely helpful for the development of newer therapeutically useful quinazoline based molecules for cancer therapy.
PubDate: 2020-12-01
- Abstract: In the present study, a novel series of quinazoline derivatives is developed for cancer therapy. All the synthesised analogues were evaluated against a panel of 60 human cancer cell lines for the antiproliferative activity. Significant and selective growth inhibition of several solid tumour cell lines such as NCI-H322M, NCI-H522 (non-small cell lung cancer), IGROV1, SK-OV-3 (ovarian cancer), TK-10 (renal cancer) and MDA-MB-468 (breast cancer) was observed. Further, all the new amide analogues strongly inhibited EGFR in low nanomolar range with morpholino quinazoline 10 producing activity (IC50 = 6.12 nM) comparable to standard drugs erlotinib and gefitinib. In addition, western blot analysis depicted inhibition of phosphorylation of EGFR by compounds 10 and 11 in MDA-MB-468 cells at 10 µM. Molecular docking studies showed the strong binding interactions with the active site of the EGFR protein. The current investigation could be extremely helpful for the development of newer therapeutically useful quinazoline based molecules for cancer therapy.
- Design, synthesis and biological evaluation of novel 1,5-disubstituted
isatin derivatives as antitumor agents- Abstract: Isatin (1H-indole-2,3-dione) was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. Here, we described the synthesis of a novel series of 1,5-disubstituted isatin derivatives with 2-indolinone scaffold as antitumor agents. Most of the synthesized compounds revealed potent antiproliferative effects in mantle cell lymphoma (MCL) cell lines, among which 7l possessed promising activities with IC50 values ranging from 0.4 to 1.3 μM. Following flow cytometric analysis, compound 7l efficiently arrested the cell cycle at G2/M phase, and induced apoptosis. Thus, this study shows promise in therapeutics of 1,5-disubstituted isatin derivatives in MCL and provides novel potential and efficient antitumor agents.
PubDate: 2020-12-01
- Abstract: Isatin (1H-indole-2,3-dione) was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. Here, we described the synthesis of a novel series of 1,5-disubstituted isatin derivatives with 2-indolinone scaffold as antitumor agents. Most of the synthesized compounds revealed potent antiproliferative effects in mantle cell lymphoma (MCL) cell lines, among which 7l possessed promising activities with IC50 values ranging from 0.4 to 1.3 μM. Following flow cytometric analysis, compound 7l efficiently arrested the cell cycle at G2/M phase, and induced apoptosis. Thus, this study shows promise in therapeutics of 1,5-disubstituted isatin derivatives in MCL and provides novel potential and efficient antitumor agents.
- New Pt(II) complexes with 3 ’ -methyl tetrahydro-4 H -thiopyranspiro-5
’ -hydantoin: synthesis, theoretical and cytotoxic investigation- Abstract: Three new platinum complexes with chemical formulas cis-[PtL2Cl2], cis-[PtL2I2] and cis-[PtL(NH3)Cl2], where L is 3’-methyl-4-thio-1H-tetrahydropyranspiro-5’-hydantoin were synthesized and studied. The spectral and theoretical investigations proved that ligand coordinates through sulfur atom from tetrahydrothiopyrane fragment by monodentate manner with platinum ion. The newly synthesized compounds were tested for cytotoxic activity in vitro against four human tumor cell lines using MTT dye-reduction assay for cell viability. The tested compounds displayed cytotoxic effects in a concentration-dependent manner. Complex 2 as well as complex 3 have similar cytotoxicity to that of the prototype drug cisplatin on colon adenocarcinoma model HT-29.
PubDate: 2020-12-01
- Abstract: Three new platinum complexes with chemical formulas cis-[PtL2Cl2], cis-[PtL2I2] and cis-[PtL(NH3)Cl2], where L is 3’-methyl-4-thio-1H-tetrahydropyranspiro-5’-hydantoin were synthesized and studied. The spectral and theoretical investigations proved that ligand coordinates through sulfur atom from tetrahydrothiopyrane fragment by monodentate manner with platinum ion. The newly synthesized compounds were tested for cytotoxic activity in vitro against four human tumor cell lines using MTT dye-reduction assay for cell viability. The tested compounds displayed cytotoxic effects in a concentration-dependent manner. Complex 2 as well as complex 3 have similar cytotoxicity to that of the prototype drug cisplatin on colon adenocarcinoma model HT-29.
- Synthesis, biological evaluation and molecular docking studies of
Combretastatin A-4 phosphoramidates as novel anticancer prodrugs- Abstract: A new series of CA4P analogs (5a-g, 6a-g) has been designed and effectively synthesized via a one-pot reaction from Combretastatin A-4/Erianin, commercially available amino acid esters and phenyl dichlorophosphate. To establish new candidates with anticancer activity, the in vitro antiproliferative effect of these compounds was measured by the CCK8 method on different cancer cell lines such as human liver caricinoma (HepG2), cervical cancer (HeLa) and colorectal carcinoma (HCT-116). The structure-activity relationships between CA4P outgrowth-promoting activity and its analogs suggested that the biaryl structure linked with double bond in Part A and the steric effect at the position α-carbon atom in the amino acid ester moiety (Part B) are essential for affecting the in vitro proliferation inhibitory activity of CA4P analogs. Additionally, the results of biological activity and molecular docking simulation showed that the vast majority of these novel Phosphoramidate derivatives exhibited potent anti-cancer activities.
PubDate: 2020-12-01
- Abstract: A new series of CA4P analogs (5a-g, 6a-g) has been designed and effectively synthesized via a one-pot reaction from Combretastatin A-4/Erianin, commercially available amino acid esters and phenyl dichlorophosphate. To establish new candidates with anticancer activity, the in vitro antiproliferative effect of these compounds was measured by the CCK8 method on different cancer cell lines such as human liver caricinoma (HepG2), cervical cancer (HeLa) and colorectal carcinoma (HCT-116). The structure-activity relationships between CA4P outgrowth-promoting activity and its analogs suggested that the biaryl structure linked with double bond in Part A and the steric effect at the position α-carbon atom in the amino acid ester moiety (Part B) are essential for affecting the in vitro proliferation inhibitory activity of CA4P analogs. Additionally, the results of biological activity and molecular docking simulation showed that the vast majority of these novel Phosphoramidate derivatives exhibited potent anti-cancer activities.
- Phytochemistry, pharmacology and medicinal uses of Cola (Malvaceae)
family: a review- Abstract: Cola belongs to the family Malvaceae and contains 125 Cola plants. Among the Cola species, Cola acuminata and Cola nitida are the most studied for their pharmacology effects. Cola contains phytochemicals such as alkaloids, caffeine, theobromine, theophylline, quinic acid, chlorogenic acid, purine, (−)-epicatechin, (+)-catechin, sterols, anthraquinones, flavonoid glycosides, cardenolides, tannins, rostratanic acid, bauerenol, lupeol, acotatarone A, lignoceric acid, betulinic acid, friedelanone, friedelan, stigmasterol, and nonanedioc acid, among others. These secondary metabolites are responsible for the various pharmacological activities such as antioxidant, antibacterial, antifungal, antimalarial, anti-inflammatory, antidiabetic, antidiarrheal, antiviral, anticancer, antimycobacterium, and antiatherosclerotic and hypolipidaemic. Economically, Cola has been used in both manufacturing and pharmaceutical industries to produce energy drinks, flavoring agents, wine, chocolates, animal feeds, medicine, food, disinfectant, pomade, organic fertilizers, candles, detergents, and as dyes in textiles. This review work aimed to review the report published up to 2019 describing the traditional uses, phytochemistry, and pharmacological activities of Cola species.
PubDate: 2020-12-01
- Abstract: Cola belongs to the family Malvaceae and contains 125 Cola plants. Among the Cola species, Cola acuminata and Cola nitida are the most studied for their pharmacology effects. Cola contains phytochemicals such as alkaloids, caffeine, theobromine, theophylline, quinic acid, chlorogenic acid, purine, (−)-epicatechin, (+)-catechin, sterols, anthraquinones, flavonoid glycosides, cardenolides, tannins, rostratanic acid, bauerenol, lupeol, acotatarone A, lignoceric acid, betulinic acid, friedelanone, friedelan, stigmasterol, and nonanedioc acid, among others. These secondary metabolites are responsible for the various pharmacological activities such as antioxidant, antibacterial, antifungal, antimalarial, anti-inflammatory, antidiabetic, antidiarrheal, antiviral, anticancer, antimycobacterium, and antiatherosclerotic and hypolipidaemic. Economically, Cola has been used in both manufacturing and pharmaceutical industries to produce energy drinks, flavoring agents, wine, chocolates, animal feeds, medicine, food, disinfectant, pomade, organic fertilizers, candles, detergents, and as dyes in textiles. This review work aimed to review the report published up to 2019 describing the traditional uses, phytochemistry, and pharmacological activities of Cola species.
- Organotin (IV) complexes from Schiff bases ligands based on
2-amino-3-hydroxypyridine: synthesis, characterization, and cytotoxicity- Abstract: A multicomponent reaction was used as a synthetic strategy to prepare organotin (IV) complexes, 2-amino-3-hydroxypyridine, saliciladehydes 5-R-substituted (H, CH3, OCH3, C(CH)3, F, Cl, Br, I, NO2), and dibutyltin(IV) oxide were used as starting materials. The complexes were analyzed by IR, UV–Visible, MS, NMR of 1H, 13C, 119Sn. The complex 3a was structurally identified by X-ray crystallography, which revealed a dimeric arrangement where the tin atom possess a distorted hexacoordinated environment in which the deprotonated phenolic oxygen atoms and the nitrogen atom of the azomethine from the ligand are coordinated to the metallic center, and one of the phenoxy oxygens bridges with the tin through an intermolecular interaction forming a planar Sn2O2 core. As strategy of molecular design, isosteric and bioisosteric replacement of halogens were employed. All organotin compounds were assessed for their in vitro cytotoxic activity on cancer cell lines K‐562 (chronic myelogenous leukemia), U‐251 (glioblastoma), HCT‐15 (human colorectal cancer), MCF‐7, MDA-MB-231 (human breast cancer), and SKLU‐1 (non‐small‐cell lung cancer). They evidenced an elevated cytotoxic activity, and the inhibitory percentage values stated higher activity than the cis-platin. The K-562 and MDA-MB-231 cells were more sensitive to organotin (IV) complexes than HCT-15 and MCF-7. The organotin (IV) compounds were also tested in vivo for brine shrimp lethality to examine their toxic properties.
PubDate: 2020-12-01
- Abstract: A multicomponent reaction was used as a synthetic strategy to prepare organotin (IV) complexes, 2-amino-3-hydroxypyridine, saliciladehydes 5-R-substituted (H, CH3, OCH3, C(CH)3, F, Cl, Br, I, NO2), and dibutyltin(IV) oxide were used as starting materials. The complexes were analyzed by IR, UV–Visible, MS, NMR of 1H, 13C, 119Sn. The complex 3a was structurally identified by X-ray crystallography, which revealed a dimeric arrangement where the tin atom possess a distorted hexacoordinated environment in which the deprotonated phenolic oxygen atoms and the nitrogen atom of the azomethine from the ligand are coordinated to the metallic center, and one of the phenoxy oxygens bridges with the tin through an intermolecular interaction forming a planar Sn2O2 core. As strategy of molecular design, isosteric and bioisosteric replacement of halogens were employed. All organotin compounds were assessed for their in vitro cytotoxic activity on cancer cell lines K‐562 (chronic myelogenous leukemia), U‐251 (glioblastoma), HCT‐15 (human colorectal cancer), MCF‐7, MDA-MB-231 (human breast cancer), and SKLU‐1 (non‐small‐cell lung cancer). They evidenced an elevated cytotoxic activity, and the inhibitory percentage values stated higher activity than the cis-platin. The K-562 and MDA-MB-231 cells were more sensitive to organotin (IV) complexes than HCT-15 and MCF-7. The organotin (IV) compounds were also tested in vivo for brine shrimp lethality to examine their toxic properties.
- A convenient synthesis, reactions and biological evaluation of novel
pyrazolo[3,4- b ]selenolo[3,2- e ]pyrazine heterocycles as potential
anticancer and antimicrobial agents- Abstract: A novel series of 5-amino-6-substituted-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]pyrazines (3a–e) was synthesized by the reaction of the chloro pyrazolo[3,4-b]pyrazine carbonitrile 1 with selenium element in the presence of sodium borohydride and ethanol, followed by the reaction with α-halo alkylating agents to produce the selanyl-alkylated derivatives 2a–e. The latter compounds underwent Thorpe-Ziegler cyclization upon heating with ethanolic sodium ethoxide solution to afford the target selenolopyrazolopyrazine compounds. The 5-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]pyrazine-6-carboxamide (3b) was used as a versatile precursor for synthesis of new heterocyclic fused to the pyrazoloselenolopyrazine moiety namely: pyrimidine and imidazopyrimidine. Assignment of the chemical structures for the newly synthesized compounds was confirmed on the bases of elemental and spectral techniques including FT-IR, 1H NMR, 13C NMR, and mass spectra. Furthermore, certain compounds were screened for their antimicrobial activity which revealed remarkable activities against various pathogenic strains of bacteria and fungi. Alternatively, some of these compounds exhibited promising anticancer action against some colon and breast cancer cells.
PubDate: 2020-12-01
- Abstract: A novel series of 5-amino-6-substituted-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]pyrazines (3a–e) was synthesized by the reaction of the chloro pyrazolo[3,4-b]pyrazine carbonitrile 1 with selenium element in the presence of sodium borohydride and ethanol, followed by the reaction with α-halo alkylating agents to produce the selanyl-alkylated derivatives 2a–e. The latter compounds underwent Thorpe-Ziegler cyclization upon heating with ethanolic sodium ethoxide solution to afford the target selenolopyrazolopyrazine compounds. The 5-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]pyrazine-6-carboxamide (3b) was used as a versatile precursor for synthesis of new heterocyclic fused to the pyrazoloselenolopyrazine moiety namely: pyrimidine and imidazopyrimidine. Assignment of the chemical structures for the newly synthesized compounds was confirmed on the bases of elemental and spectral techniques including FT-IR, 1H NMR, 13C NMR, and mass spectra. Furthermore, certain compounds were screened for their antimicrobial activity which revealed remarkable activities against various pathogenic strains of bacteria and fungi. Alternatively, some of these compounds exhibited promising anticancer action against some colon and breast cancer cells.
- Synthesis of pyrazinamide analogues and their antitubercular bioactivity
- Abstract: The Yamaguchi reaction is widely and generally applied to synthesize esters and lactones. It involves 2,4,6-trichlorobenzoyl chloride as the Yamaguchi reagent, 4-dimethylaminopyridine, and triethylamine. Pyrazinamide is a crucial first-line drug for tuberculosis treatment, therefore their analogues are interesting in organic synthesis. In general, the synthesis pyrazinamide analogues involve reaction of pyrazine-2-carboxylic acids with thionyl chloride to yield the corresponding acyl chlorides, which on treatment with amines gave pyrazine-2-carboxamides. However, thionyl chloride is listed under the Chemical Weapons Convention and releases toxic sulfur oxide when react with carboxylic acid. We successfully synthesized series of pyrazinamide analogues using the Yamaguchi reaction. The synthesis involved reaction of pyrazine-2-carboxylic acid with various aliphatic and aromatic amines in the presence of Yamaguchi reagent and 4-dimethylaminopyridine. The yield of the pyrazine-2-carboxamides and the reaction time depended on the type of the amine (aliphatic vs aromatic), substitution pattern, and number of substituents on the aromatic amines. N-(4-chlorophenyl)pyrazine-2-carboxamides can be prepared by this method in 81% yield; N-(2-ethylhexyl)pyrazine-2-carboxamide and N-(4-fluorobenzyl)pyrazine-2-carboxamide showed the best activity against Mycobacterium tuberculosis H37Rv (<6.25 μg/mL). This result could lead to find more active pyrazinamide analogues.
PubDate: 2020-12-01
- Abstract: The Yamaguchi reaction is widely and generally applied to synthesize esters and lactones. It involves 2,4,6-trichlorobenzoyl chloride as the Yamaguchi reagent, 4-dimethylaminopyridine, and triethylamine. Pyrazinamide is a crucial first-line drug for tuberculosis treatment, therefore their analogues are interesting in organic synthesis. In general, the synthesis pyrazinamide analogues involve reaction of pyrazine-2-carboxylic acids with thionyl chloride to yield the corresponding acyl chlorides, which on treatment with amines gave pyrazine-2-carboxamides. However, thionyl chloride is listed under the Chemical Weapons Convention and releases toxic sulfur oxide when react with carboxylic acid. We successfully synthesized series of pyrazinamide analogues using the Yamaguchi reaction. The synthesis involved reaction of pyrazine-2-carboxylic acid with various aliphatic and aromatic amines in the presence of Yamaguchi reagent and 4-dimethylaminopyridine. The yield of the pyrazine-2-carboxamides and the reaction time depended on the type of the amine (aliphatic vs aromatic), substitution pattern, and number of substituents on the aromatic amines. N-(4-chlorophenyl)pyrazine-2-carboxamides can be prepared by this method in 81% yield; N-(2-ethylhexyl)pyrazine-2-carboxamide and N-(4-fluorobenzyl)pyrazine-2-carboxamide showed the best activity against Mycobacterium tuberculosis H37Rv (<6.25 μg/mL). This result could lead to find more active pyrazinamide analogues.
- Radiosynthesis of [ 11 C]EI1 for imaging EZH2 using positron emission
tomography- Abstract: Enhancer of zeste homolog 2 (EZH2) is responsible for the methylation of lysine 27 of histone H3 (H3K27) leading to transcriptional repression. Consequently, EZH2 is related with several diseases including cancers, as overexpressed EZH2 can down-regulate cancer suppressor genes. Therefore, EZH2 became a promising target for cancer treatment and diagnosis and in vivo imaging of EZH2 is critical for diagnosis and treatment monitor. In the present work, we radiolabeled a specific inhibitor of EZH2, [11C]EI1, investigated its pharmacokinetics and performed micro PET/CT imaging. Results showed that the half-life of the [11C]EI1 in blood was 3.4 min. Micro PET/CT imaging showed that the [11C]EI1 can enter the major organs including liver, stomach, and intestine and can be blocked by the unlabeled EI1 resulting in a significant distinct between apparent distribution volumes (Vd, 2.8 mL for blocking versus 17.4 ml for baseline), which validated the specific affinity of the [11C]EI1 against EZH2 and illustrated the distribution of EZH2 in major organs. The results indicated that the [11C]EI1 can be a tracer for EZH2 PET imaging used in diagnosis and therapy monitor of EZH2 related diseases especially cancers.
PubDate: 2020-12-01
- Abstract: Enhancer of zeste homolog 2 (EZH2) is responsible for the methylation of lysine 27 of histone H3 (H3K27) leading to transcriptional repression. Consequently, EZH2 is related with several diseases including cancers, as overexpressed EZH2 can down-regulate cancer suppressor genes. Therefore, EZH2 became a promising target for cancer treatment and diagnosis and in vivo imaging of EZH2 is critical for diagnosis and treatment monitor. In the present work, we radiolabeled a specific inhibitor of EZH2, [11C]EI1, investigated its pharmacokinetics and performed micro PET/CT imaging. Results showed that the half-life of the [11C]EI1 in blood was 3.4 min. Micro PET/CT imaging showed that the [11C]EI1 can enter the major organs including liver, stomach, and intestine and can be blocked by the unlabeled EI1 resulting in a significant distinct between apparent distribution volumes (Vd, 2.8 mL for blocking versus 17.4 ml for baseline), which validated the specific affinity of the [11C]EI1 against EZH2 and illustrated the distribution of EZH2 in major organs. The results indicated that the [11C]EI1 can be a tracer for EZH2 PET imaging used in diagnosis and therapy monitor of EZH2 related diseases especially cancers.
- Antioxidant, antiproliferative, and acetylcholinesterase inhibition
activity of amino alcohol derivatives from 1,4-naphthoquinone- Abstract: Natural and synthetic naphthoquinones have demonstrated numerous biological activities; therefore, they provide an interesting scaffold for medicinal chemists in the search for new drugs. A series of amino alcohol derivatives from 1,4-naphthoquinone with a free (2a–e) and acetylated (3a–d) hydroxyl group were synthesized, characterized, and evaluated as antioxidant agents employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compound 3d showed the better result with 51.52% of antioxidant activity at 1 mg/mL, while in ABTS·+ was 2e (47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products 2a, 2c, and 2e against cervix line HeLa, with 50% growth inhibition (GI50) of 5.6, 15.0, and 17.0 μM, respectively. All synthesized compounds presented varying degrees of response, some of them with similar results compared with the positive control 5-fluorouracil. AChE inhibition of the products was not as strong as the positive control galantamine; the most potent compound was 2e with a 50% inhibitory concentration (IC50) of 0.0586 mM, followed by 2a (0.0902 mM). No inhibition in the evaluated concentrations was observed for products 2d and 3a-d. Docking of 2a and 2e was realized against AChE in order to gain insight into the interactions made between them and the enzyme residues in its catalytic gorge. In silico calculations for all synthesized products showed their drug-like properties. Alcohol derivatives, specially 2a and 2e, could be further derivatized in the search for new and improved drugs.
PubDate: 2020-11-01
- Abstract: Natural and synthetic naphthoquinones have demonstrated numerous biological activities; therefore, they provide an interesting scaffold for medicinal chemists in the search for new drugs. A series of amino alcohol derivatives from 1,4-naphthoquinone with a free (2a–e) and acetylated (3a–d) hydroxyl group were synthesized, characterized, and evaluated as antioxidant agents employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compound 3d showed the better result with 51.52% of antioxidant activity at 1 mg/mL, while in ABTS·+ was 2e (47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products 2a, 2c, and 2e against cervix line HeLa, with 50% growth inhibition (GI50) of 5.6, 15.0, and 17.0 μM, respectively. All synthesized compounds presented varying degrees of response, some of them with similar results compared with the positive control 5-fluorouracil. AChE inhibition of the products was not as strong as the positive control galantamine; the most potent compound was 2e with a 50% inhibitory concentration (IC50) of 0.0586 mM, followed by 2a (0.0902 mM). No inhibition in the evaluated concentrations was observed for products 2d and 3a-d. Docking of 2a and 2e was realized against AChE in order to gain insight into the interactions made between them and the enzyme residues in its catalytic gorge. In silico calculations for all synthesized products showed their drug-like properties. Alcohol derivatives, specially 2a and 2e, could be further derivatized in the search for new and improved drugs.
- Ionophoric polyphenols are permeable to the blood–brain barrier,
interact with human serum albumin and Calf Thymus DNA, and inhibit AChE
enzymatic activity- Abstract: Alzheimer’s disease (AD) is the most common form of dementia that affects more than 40 million people around the world. The incidence is expected to rapidly increase due to the lack of any effective treatment. In previous work we synthesized a family of five ionophoric polyphenols (compounds 1–5) that targeted important aspects related to AD, such as the toxic aggregation of amyloid-β peptides, the production of reactive oxygen species, or the excessive presence of Cu2+ ions. Here, in order to gain insights into their potential therapeutic value, we have tested the ability of compounds 1–5 to cross the blood–brain barrier (BBB), to interact with human serum albumin (HSA) and Calf Thymus (ct) DNA, and to inhibit acetylcholinesterase (AChE). We performed BBB permeability and efflux mechanisms studies by means of the in vitro parallel artificial membrane permeability assay (PAMPA-BBB) and several in silico methods, while fluorescence, UV–visible, and circular dichroism spectroscopies were used to determine their ability to interact with HSA and ctDNA. Our results show that all five ionophoric polyphenols can effectively cross the BBB, and can form adducts with both HSA and ctDNA through one binding site and with association constants ranging from 104 to 106 M−1, while still maintaining levels of unbound drug to protein within therapeutic range. Docking and molecular dynamics simulations show that the ionophoric polyphenols preferably bind the hydrophobic cavities of the subdomain IIA of HSA, as many other pharmaceuticals do, with predicted affinities that correlate well with experimental results obtained by spectroscopic techniques. In addition, structurally related compounds 1, 2, and 4 were found to be moderate in vitro AChE inhibitors by interacting with several residues of the active site of the enzyme, as revealed by docking and molecular dynamics simulations. Overall, our results suggest that HSA could be an efficient transport mechanism of the compounds in the bloodstream until reaching the brain, where they could effectively cross the BBB and exert their anti-AD activity, including AChE inhibition. DNA interactions similar to natural resveratrol could in part explain the previously reported nontoxic behavior of the compounds.
PubDate: 2020-11-01
- Abstract: Alzheimer’s disease (AD) is the most common form of dementia that affects more than 40 million people around the world. The incidence is expected to rapidly increase due to the lack of any effective treatment. In previous work we synthesized a family of five ionophoric polyphenols (compounds 1–5) that targeted important aspects related to AD, such as the toxic aggregation of amyloid-β peptides, the production of reactive oxygen species, or the excessive presence of Cu2+ ions. Here, in order to gain insights into their potential therapeutic value, we have tested the ability of compounds 1–5 to cross the blood–brain barrier (BBB), to interact with human serum albumin (HSA) and Calf Thymus (ct) DNA, and to inhibit acetylcholinesterase (AChE). We performed BBB permeability and efflux mechanisms studies by means of the in vitro parallel artificial membrane permeability assay (PAMPA-BBB) and several in silico methods, while fluorescence, UV–visible, and circular dichroism spectroscopies were used to determine their ability to interact with HSA and ctDNA. Our results show that all five ionophoric polyphenols can effectively cross the BBB, and can form adducts with both HSA and ctDNA through one binding site and with association constants ranging from 104 to 106 M−1, while still maintaining levels of unbound drug to protein within therapeutic range. Docking and molecular dynamics simulations show that the ionophoric polyphenols preferably bind the hydrophobic cavities of the subdomain IIA of HSA, as many other pharmaceuticals do, with predicted affinities that correlate well with experimental results obtained by spectroscopic techniques. In addition, structurally related compounds 1, 2, and 4 were found to be moderate in vitro AChE inhibitors by interacting with several residues of the active site of the enzyme, as revealed by docking and molecular dynamics simulations. Overall, our results suggest that HSA could be an efficient transport mechanism of the compounds in the bloodstream until reaching the brain, where they could effectively cross the BBB and exert their anti-AD activity, including AChE inhibition. DNA interactions similar to natural resveratrol could in part explain the previously reported nontoxic behavior of the compounds.
- Aryl-enclosed polyketides from mangrove sediment associated bacterium
Bacillus amyloliquefaciens attenuating pro-inflammatory 5-lipoxygenase- Abstract: Two aryl-enclosed polyketides were identified from the ethyl acetate extract of mangrove sediment associated bacterium Bacillus amyloliquefaciens, and were characterized as 1-(8-hydroxy-1-oxoisochroman-3-yl)propyl 4′-(6′-hydroxy-8′-oxotetrahydrofuran-5′-yl)acetate (compound 1) and 6′a-(3′-(1′-(8-hydroxy-1-oxoisochroman-3-yl)propoxy)-3′-oxoethyl)-8′-oxotetrahydrofuran-6′-yl butyrate (compound 2) by detailed spectroscopic techniques encompassing two-dimensional nuclear magnetic resonance and mass spectroscopic experiments. Polyketide compound 2 bearing oxotetrahydrofuran-6′-yl butyrate moiety exhibited potential antioxidant activities against the free radicals, 2,2-diphenyl-1-picrylhydrazyl radical and 2,2′-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (IC50 1.01 and 1.22 mM, respectively), and were found to be significantly greater than those displayed by polyketide 1 and standard (α-tocopherol IC50 1.45–1.63 mM, p < 0.05). Compound 2 also exhibited greater anti-inflammatory properties as determined by 5-LOX inhibitory assay (IC50 1.11 mM) than those displayed by compound 1 (IC50 1.23 mM) and standard (ibuprofen IC50 4.50 mM). Greater electronic parameters of compound 2 could further support its greater bioactive potentials.
PubDate: 2020-11-01
- Abstract: Two aryl-enclosed polyketides were identified from the ethyl acetate extract of mangrove sediment associated bacterium Bacillus amyloliquefaciens, and were characterized as 1-(8-hydroxy-1-oxoisochroman-3-yl)propyl 4′-(6′-hydroxy-8′-oxotetrahydrofuran-5′-yl)acetate (compound 1) and 6′a-(3′-(1′-(8-hydroxy-1-oxoisochroman-3-yl)propoxy)-3′-oxoethyl)-8′-oxotetrahydrofuran-6′-yl butyrate (compound 2) by detailed spectroscopic techniques encompassing two-dimensional nuclear magnetic resonance and mass spectroscopic experiments. Polyketide compound 2 bearing oxotetrahydrofuran-6′-yl butyrate moiety exhibited potential antioxidant activities against the free radicals, 2,2-diphenyl-1-picrylhydrazyl radical and 2,2′-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (IC50 1.01 and 1.22 mM, respectively), and were found to be significantly greater than those displayed by polyketide 1 and standard (α-tocopherol IC50 1.45–1.63 mM, p < 0.05). Compound 2 also exhibited greater anti-inflammatory properties as determined by 5-LOX inhibitory assay (IC50 1.11 mM) than those displayed by compound 1 (IC50 1.23 mM) and standard (ibuprofen IC50 4.50 mM). Greater electronic parameters of compound 2 could further support its greater bioactive potentials.
- Identification of potential anti-inflammatory and melanoma cytotoxic
compounds from Aegiceras corniculatum- Abstract: Many chemicals found in mangroves reportedly exhibit potent anticancer, antibacterial, anti-inflammatory, antioxidant, and antitumor properties. Several of such compounds include feature unique structures and display interesting pharmacological effects. Few medicinal mangrove plants from Vietnam have been characterized with regard to their chemical constituents. Aegiceras corniculatum (L.) Blanco is a mangrove shrub that exhibits activity against various types of cancer. To identify new secondary metabolites and determine the source(s) of biological activity in Vietnamese medicinal mangrove plants, the chemical constituents of A. corniculatum were isolated, and their structures were appropriately established using common spectroscopic methods (1D and 2D-NMR, IR, HR-ESI-MS), and by producing derivatives by chemical reactions. Complementarily, it is worth noting, that the anti-inflammatory effects of the isolated compounds were investigated by measuring the production of pro-inflammatory cytokines IL-12 p40, IL-6, and TNF-α in lipopolysaccharide-stimulated bone marrow-derived dendritic cells; in this sense, the target compounds 2 and 3 were potent inhibitors of cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Furthermore, compounds 1 and 4 strongly promoted apoptosis of B16F10 melanoma cells. It is convenient to highlight, that the obtained results suggest that saponins from A. corniculatum could be potential candidates for treating cancer and inflammatory illnesses.
PubDate: 2020-11-01
- Abstract: Many chemicals found in mangroves reportedly exhibit potent anticancer, antibacterial, anti-inflammatory, antioxidant, and antitumor properties. Several of such compounds include feature unique structures and display interesting pharmacological effects. Few medicinal mangrove plants from Vietnam have been characterized with regard to their chemical constituents. Aegiceras corniculatum (L.) Blanco is a mangrove shrub that exhibits activity against various types of cancer. To identify new secondary metabolites and determine the source(s) of biological activity in Vietnamese medicinal mangrove plants, the chemical constituents of A. corniculatum were isolated, and their structures were appropriately established using common spectroscopic methods (1D and 2D-NMR, IR, HR-ESI-MS), and by producing derivatives by chemical reactions. Complementarily, it is worth noting, that the anti-inflammatory effects of the isolated compounds were investigated by measuring the production of pro-inflammatory cytokines IL-12 p40, IL-6, and TNF-α in lipopolysaccharide-stimulated bone marrow-derived dendritic cells; in this sense, the target compounds 2 and 3 were potent inhibitors of cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Furthermore, compounds 1 and 4 strongly promoted apoptosis of B16F10 melanoma cells. It is convenient to highlight, that the obtained results suggest that saponins from A. corniculatum could be potential candidates for treating cancer and inflammatory illnesses.
- Quercetin and cervical cancer: a view of great scope
- Abstract: Cervical cancer (CC) is the most common gynecological cancer and is one of the results of high-risk HPV infection. Recent statistics demonstrate that 90% of cervical cancer cases are diagnosed in low- and middle-income countries. These results are observed due to the poor sanitation and lack of proper preventive strategies. Quercetin is a plant compound with a great number of beneficial properties which increasing the level of sanitation or acting as a preventive agent are not of its capabilities; however, what quercetin is capable of is preventing the cancer from progression in CC patients. Cell proliferation, growth, viability, survival, and migration are just a limited number of cellular processes which are prone to be affected by quercetin. In this review, we have considered each distinct role of quercetin on cellular and molecular processes, occurring as a consequence of becoming cancerous, in the cells of uterine cervix. We look forward to attract the attention of scientific community to this marvelous agent in order to help CC patients from taking expensive, toxic, and risky common therapeutic methods used for treating early to metastatic cervical cancer.
PubDate: 2020-09-10
- Abstract: Cervical cancer (CC) is the most common gynecological cancer and is one of the results of high-risk HPV infection. Recent statistics demonstrate that 90% of cervical cancer cases are diagnosed in low- and middle-income countries. These results are observed due to the poor sanitation and lack of proper preventive strategies. Quercetin is a plant compound with a great number of beneficial properties which increasing the level of sanitation or acting as a preventive agent are not of its capabilities; however, what quercetin is capable of is preventing the cancer from progression in CC patients. Cell proliferation, growth, viability, survival, and migration are just a limited number of cellular processes which are prone to be affected by quercetin. In this review, we have considered each distinct role of quercetin on cellular and molecular processes, occurring as a consequence of becoming cancerous, in the cells of uterine cervix. We look forward to attract the attention of scientific community to this marvelous agent in order to help CC patients from taking expensive, toxic, and risky common therapeutic methods used for treating early to metastatic cervical cancer.
- What are the drugs having potential against COVID-19'
- Abstract: A disease emerged in the city of Wuhan, Hubei Province, Central China in the last month of 2019. It was pneumonia caused by a newly emerged coronavirus called COVID-19, later. Coronaviruses are enveloped RNA viruses belong to the Betacoronavirus family and infected birds, humans, and other mammals. In March 2020, the World Health Organization declared the COVID-19 outbreak could be characterized as a global pandemic because the disease spread, and a large number of people were infected and died in many countries on different continents by virtue of this new virus. Now, intensive work is underway about the pathogenic mechanisms and epidemiological properties of COVID-19, and a great effort is made to develop effective specific therapeutic drugs, vaccines, and/or treatment strategies against these diseases. Herein, we have focused on all treatment options available against COVID-19 pneumonia in this text.
PubDate: 2020-09-10
- Abstract: A disease emerged in the city of Wuhan, Hubei Province, Central China in the last month of 2019. It was pneumonia caused by a newly emerged coronavirus called COVID-19, later. Coronaviruses are enveloped RNA viruses belong to the Betacoronavirus family and infected birds, humans, and other mammals. In March 2020, the World Health Organization declared the COVID-19 outbreak could be characterized as a global pandemic because the disease spread, and a large number of people were infected and died in many countries on different continents by virtue of this new virus. Now, intensive work is underway about the pathogenic mechanisms and epidemiological properties of COVID-19, and a great effort is made to develop effective specific therapeutic drugs, vaccines, and/or treatment strategies against these diseases. Herein, we have focused on all treatment options available against COVID-19 pneumonia in this text.
- Anti-inflammatory polyoxygenated furanocembranoids, salmacembranes A–B
from the sea urchin Salmacis bicolor attenuate pro-inflammatory
cyclooxygenases and lipoxygenase- Abstract: Two undescribed polyoxygenated furanocembranoid derivatives, methyl 15-(9-hydroxy-8-methoxy-2,12-dimethyl-15-oxa-bicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-3-yl)propanoate (salmacembrane A) and 1-(16-methyl-2,16-dihydrofuran)-8-methoxy-12-methyl-20-oxabicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-9-ol (salmacembrane B), were isolated from the organic extract of sea urchin Salmacis bicolor (family Temnopleuridae) by extensive chromatographic purification. Their structures were elucidated using detailed spectroscopic evidence. Salmacembrane A displayed significantly greater attenuation property against pro-inflammatory cyclooxygenase-2 (IC50 1.71 mM) than that exhibited by salmacembrane B (IC50 1.99 mM). Salmacembrane A could potentially inhibit 5-lipoxygenase (IC50 1.87 mM) and its activity was significantly greater than that exhibited by anti-inflammatory agent ibuprofen (IC50 4.50 mM, p < 0.05). The greater selectivity index (anti-cyclooxygense-2/anti-cyclooxygense-1) of salmacembrane A (1.06) than ibuprofen (0.43) further supported higher selectivity toward pro-inflammatory isoenzyme cyclooxygenase-2. Salmacembrane A displayed higher antioxidant properties against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl (IC50 1.57 and 1.65 mM, respectively) than those exhibited by salmacembrane B (IC50 > 1.85 mM). In addition, these antioxidant activities were comparable to the standard α-tocopherol (IC50 DPPH 1.51 mM, IC50 ABTS+ 1.70 mM p < 0.05). The higher electronic parameters obtained from structure–activity relationship analysis along with greater binding affinities of salmacembrane A at the active site of cyclooxygenase-2 ascribed its potential anti-inflammatory activity.
PubDate: 2020-09-10
- Abstract: Two undescribed polyoxygenated furanocembranoid derivatives, methyl 15-(9-hydroxy-8-methoxy-2,12-dimethyl-15-oxa-bicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-3-yl)propanoate (salmacembrane A) and 1-(16-methyl-2,16-dihydrofuran)-8-methoxy-12-methyl-20-oxabicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-9-ol (salmacembrane B), were isolated from the organic extract of sea urchin Salmacis bicolor (family Temnopleuridae) by extensive chromatographic purification. Their structures were elucidated using detailed spectroscopic evidence. Salmacembrane A displayed significantly greater attenuation property against pro-inflammatory cyclooxygenase-2 (IC50 1.71 mM) than that exhibited by salmacembrane B (IC50 1.99 mM). Salmacembrane A could potentially inhibit 5-lipoxygenase (IC50 1.87 mM) and its activity was significantly greater than that exhibited by anti-inflammatory agent ibuprofen (IC50 4.50 mM, p < 0.05). The greater selectivity index (anti-cyclooxygense-2/anti-cyclooxygense-1) of salmacembrane A (1.06) than ibuprofen (0.43) further supported higher selectivity toward pro-inflammatory isoenzyme cyclooxygenase-2. Salmacembrane A displayed higher antioxidant properties against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl (IC50 1.57 and 1.65 mM, respectively) than those exhibited by salmacembrane B (IC50 > 1.85 mM). In addition, these antioxidant activities were comparable to the standard α-tocopherol (IC50 DPPH 1.51 mM, IC50 ABTS+ 1.70 mM p < 0.05). The higher electronic parameters obtained from structure–activity relationship analysis along with greater binding affinities of salmacembrane A at the active site of cyclooxygenase-2 ascribed its potential anti-inflammatory activity.
