Abstract: Repaglinide (REP) is a potent medication for treating diabetes (BCS class II) that has a low oral bioavailability of less than 55% due to its poor solubility and significant metabolism in the liver during its first pass. The objective of this study was to develop a nanocarrier system called nanostructured lipid carriers loaded with repaglinide (REP-NLCs) that provides the benefits of prolonged drug release and enhanced oral bioavailability. Conducting solubility experiments allowed for the identification of suitable lipids and surfactants for the formulation of NLCs. The REP-NLCs were synthesized using hot homogenization followed by ultrasonication procedures and subsequently analyzed for their size, zeta potential, polydispersity index (PDI), and drug entrapment efficiency (E.E). The results demonstrated that altering the lipid or surfactant type had a significant impact on the entrapment efficiencies, particle size, and release behavior of the NLCs. The average particle size varied between 59.1 ± 3.2 and 898.4 ± 40.3 nm. The particles exhibited a negative charge, with zeta potential values ranging from −32.27 ± 1.01 to −26.13 ± 7.37 mV. The in vitro release of all REP-NLC formulas exhibited a biphasic time-dependent pattern. The E.E varied between 70.11 ± 5.3 and 85.32 ± 4.6 %. REP-NLCs exhibited prolonged drug release compared to the dissolution of REP suspension.
Abstract: The antitumor properties of synthetic heterocyclic compounds are among the most powerful properties that can be made use in medicinal chemistry. More specifically, their significant cytotoxic effects against many types of human tumor cells, as well as their roles as various kinase inhibitors. In recent years, Phthalazine derivatives, have frequently attracted the interest of medicinal chemistry researchers due to their promising anticancer properties. The present study is a review of the latest advances in Phthalazine derivative-related research, with a focus on their anticancer activities as VEGFR-2 inhibitors.
Abstract: Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are enzymes that catalyze the rate-limiting step of the kynurenine pathway. Recent literature reports IDO and TDO upregulation in tumor cells leading to L-tryptophan depletion and accumulation of tryptophan metabolites. This process represents an essential mechanism for tumor-induced immunosuppression. Following the failure of Epacadostat, an IDO inhibitor, in phase 3 clinical trials, numerous studies have shifted to a dual inhibition scheme to overcome the compensation mechanism linked to TDO. Therefore, the dual inhibition of IDO and TDO using a single molecule emerges as a highly promising therapeutic approach. This comprehensive review aims to discuss the successful scaffolds of reported dual inhibitors and their inhibitory values against both enzymes. The reported active compounds have the potential to form a novel chemical class of anti-tumor immune modulator drugs.
Abstract: Pyrazolopyrimidines are composed of a pyrazole ring fused with pyrimidine moiety, unlike the imidazole moiety in purines; they are initially reported as adenosine receptor antagonists. Different methods of synthesis of substituted pyrazolo[3,4-d]pyrimidines and pyrazolo[1,5-a]pyrimidines have been reported with a survey of their biological activities especially anti-cancer activity. During the last two decades, pyrazolopyrimidines have gained great attention as biologically active compounds; they are reported to have anti-cancer activity, anti-microbial, anti-inflammatory, anti-hyperuricemia, anti-viral and anti-hypertensive activities. Researchers paid great attention to pyrazolopyrimidines due to their high anti-cancer activity, so they tried to prepare new derivatives and examine their anti-cancer activity. In this review we are going to focus on the different methods used for the synthesis of pyrazolopyrimidines, their anticancer activities as well as their reported mode of action.
Abstract: Antibiotic resistance is a growing global health threat and requires extensive research to combat this urgent problem. Phenylthiazoles, known for their diverse biological activities including anthelmintic, insecticidal, and antimicrobial properties, have recently gained particular attention as potential anti-MRSA lead compounds. This class of compounds is an established pharmacophore for the development of new antibacterial agents, particularly against multidrug-resistant bacteria such as MRSA, a notorious pathogen resistant to most first-line antibiotics. In-depth structure-activity relationship (SAR) studies of phenylthiazoles revealed two key features critical to their antibacterial activity: a nitrogen-containing head and a lipophilic tail. In this study, we aimed to reduce the lipophilicity of phenylthiazoles and improve their overall physicochemical and pharmacokinetic profiles by synthesizing a new series bearing primary amines at the phenyl-4 position. Notably, compounds 5m exhibited bactericidal activity against MRSA, exhibiting a minimum inhibitory concentration (MIC) of only 8 µg/mL against the prevalent MRSA strain USA300.
Abstract: The main purpose of this work is to establish three simple, sensitive, accurate and precise spectrophotometric methods manipulating ratio spectra for determination of molnupiravir in bulk powder and in pharmaceutical preparation in the presence of its acid-induced degradation product. Ratio derivative, ratio difference and mean centering of ratio spectra are simple, rapid and selective methods using manipulation of ratio spectra for the determination of components having overlapping spectra. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of molnupiravir in bulk powder and in pharmaceutical preparation in the presence of its acid-induced degradation product.
Abstract: The textile industry is a significant player in the global economy; however, it is known for its contribution to environmental pollution by discharging untreated wastewater containing synthetic dyes. Crystal violet is a commonly used dye in the textile industry but has a harmful effect on humans and the environment. Therefore, developing a sustainable, environmentally friendly, and cheap method for crystal violet biodegradation like microbial biodegradation is crucial. To isolate bacteria degrading crystal violet, textile effluent wastewater was collected from different dying plants in Egypt. The degradation capacity of the bacteria isolated from textile effluent was measured using a spectrophotometer. The two bacterial isolates showing maximum crystal violet degradation FSL-1 and EBA-2, were identified using 16S rRNA as Klebsiella pneumoniae and Pseudomonas oleovorans, respectively. The effect of different parameters, including incubation time, initial dye concentration, pH, temperature, carbon source, agitation, and media composition, was studied on the ability of the two isolates to degrade crystal violet. The highest degradation of 92% was observed with K. pneumoniae isolate when inoculated in MSM-Y media containing 0.01 g/L crystal violet when incubated at 37 °C for 48 h under agitated conditions and pH 7; however, complete crystal violet degradation was observed when MSM-Y was substituted with brain heart infusion broth under the same conditions. Therefore, the newly identified bacterial strains in this study can be effectively utilized for the treatment of textile effluent containing crystal violet when certain parameters are optimized.
Abstract: Green nanoparticle synthesis is gaining popularity and has been proposed instead of using physical and chemical processes. In this work, the bacterial strain Stenotrophomonas pavanii was used to produce zinc oxide nanoparticles (ZnO-NPs) in a low-cost and eco-friendly manner. The biosynthesized nanoparticles were examined using dynamic light scattering (DLS), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The ZnO nanoparticles synthesized were clean, principally round in form, and vary in size from 0.9 to 17.1 nm. In the present work, the biosynthesized ZnO nanoparticles have been used for antimicrobial applications against Gram-positive and Gram-negative bacteria, yeast, and fungi strains. ZnO NPs had better antibacterial efficacy against tested Gram-negative bacteria than they did against Gram-positive bacterial and fungal strains. The highest antimicrobial activity against Escherichia coli (28 mm) and Pseudomonas putida (29 mm). The extracellular production of zinc oxide nanoparticles from culture Stenotrophomonas pavanii showed good antibacterial activity.
Abstract: A total of twenty-six diverse actinomycetes were obtained from various regions of the Mediterranean Sea in Alexandria, Egypt. These isolates underwent primary screening against multiple Gram-positive, Gram-negative, yeast, and fungal strains. In the secondary screening, nine isolates exhibited varying degrees of activity against the tested microorganisms. Among them, isolate A7 demonstrated potent antimicrobial properties and was chosen for further investigation. Through morphological, biochemical, microscopic, and molecular identification techniques, isolate A7 was identified as Streptomyces mutabilis. The study also explored the influence of nutritional and physical factors on the antimicrobial activity of the agent generated by isolate A7. The optimal conditions for antimicrobial activity were found to be a pH value of 6, an incubation temperature of 37°C, a NaCl concentration of 4 g/L, 1.5% starch concentration, 0.4% sodium nitrate concentration, and 2.5 g/L of K2HPO4.3H2O. Additionally, 0.5 g/L of MgSO4 was incorporated into the broth media. The incubation was performed in a shaking incubator for 7 days at 150 rpm. Ethyl acetate was used in combination with thin-layer chromatography to extract and purify the antimicrobial agent. Fraction No. 6 exhibited the highest activity against the tested microorganisms. The purified compound was identified as Phenol, 2-Methoxy-4-(2-Propenyl). It displayed antimicrobial activity against various microorganisms and demonstrated significant antiviral activity without any observed cytotoxic effects on the tested cell line.
Abstract: The dipeptidyl peptidase inhibitors (DPP-4) are a class of anti-diabetics approved for the oral treatment of type 2 diabetes mellitus (DM). That act by preventing the degradation of incretin hormones: which play an important role in insulin secretion and blood glucose regulation. The DPP-4 inhibitors have the potential to offer beneficial effects beyond the improvement of glycemic control which lies with the functional ability of the DPP-4 enzyme to cleave a variety of peptides other than incretins that have established renal and cardiovascular effects. Linagliptin (Lina) is distinctive amongst gliptins because it is the only compound that can be eliminated via a non-renal pathway, so a reduction in the glomerular filtration rate doesn't require dose adjustment. In addition, Lina is the only identified DPP-4 inhibitor that has been evaluated in a multicenter randomized clinical trial designed to thoroughly evaluate cardio-renal outcomes in patients with type 2 DM. This review provides a brief overview of the current literature on the renoprotective effects of Lina in experimental models of acute and chronic kidney disease (CKD) and clinical studies and sheds some light on the underlying mechanisms of protection.
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