Field and atom-based 3D-QSAR models of chromone (1-benzopyran-4-one) derivatives as MAO inhibitors.

Monoamine oxidases (MAOs) are flavo-enzymes that aid in the oxidative deamination of neurotransmitters like dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that work by preventing the breakdown of brain neurotransmitters and regulating mood. MAO inhibitors that use the chromone (1-benzopyran-4-one) structure have been found to be quite effective in studies. The current study involves the creation of pharmacophore models, 3-D QSAR, virtual screening, and docking investigations, all of which are evaluated using various criteria. The investigation included 39 ligands that emerged pharmacophore AHRRR_1, as the best pharmacophore model with a survival score of 5.6485. The 3D QSAR investigation revealed a significant model with the values of R2 = 0.9064 and Q2 = 0.8239. Docking study revealed that compound 18 had the highest docking (-10.402 kcal/mol) score in the series and showed interactions with the essential amino acid TYR398 required for MAO inhibitory activity. ZINC compounds were screened using the created pharmacophore model, which was followed up with a virtual screening study. The ZINC compounds with the best XP docking scores are ZINC03113255, ZINC07777127, ZINC05166353 and ZINC09341502 (with docking scores -10.021, -9.486, -8.031 and -7.792 kcal/mol, respectively). ZINC03113255, which showed the best score, has binding interactions with amino acid residues, TYR326, TYR398 and LYS296 of monoamine oxidase B. The ADME analysis demonstrated the compound's drug-like characteristics. The findings of this study may be used in the development of chromone compounds that target the MAO inhibitor.Communicated by Ramaswamy H. Sarma.

Structural aspects of triazole derivatives as HSP90 inhibitors for the treatment of cancer: in silico studies.

HSP90, one important class of chaperons has been intensively investigated as a promising and novel class of drug target for cancer therapy from the past few decades. A series of 2-((4-resorcinolyl)-5-aryl-1, 2, 3-triazol-1-yl) acetate derivatives were taken in the present study for the generation of pharmacophore based models, predictive 3 D-QSAR models, docking and ZINC screening studies against HSP90. The investigation included 30 ligands which emerged DHRRR_1 having survival score of 5.59 was found the most effective pharmacophore model. The generated third PLS factor includes a model with significant Q2, R2, and R2 CV values as 0.62, 0.77, and 0.50, respectively. The molecular docking studies against HSP90 showed interactions with important amino acids such as GLY-97, ASN-106, THR-184, ASN-51, PHE-138 and SER-52 required for HSP90 inhibitory activity. According to the docking analysis compound 34 was the top scoring compound, had a docking score of -10.98 from the series and showed interactions with amino acids likeASP-93, GLY-97, AND ASP-102. Using pharmacophore characteristics, the virtual screening investigation was carried out and DHRRR_1 showed the potential ZINC compounds. The ZINC compounds ZINC72417069 and ZINC77522480 showed best XP docking scores (-8.205 and -7.103 consecutively) and the top-scoring compound ZINC72417069 displayed amino acid binding affinity with GLY-97, ASN-106, and THR-184 against HSP90, PDB ID: 2xjx. These ZINC compounds can be used as target for HSP90. The result of the study may further help to the scientist for the design and development of potential HSP90 inhibitors.

An Investigative Review for Pharmaceutical Analysis of Fenofibrate.

HMG-CoA reductase inhibitors (statins), lipoprotein lipase activators (PPARα agonists) or fibrates are commonly used for controlling increased lipid levels in hyperlipidemia. Fenofibrate (FEN) belongs to the second generation prodrug fibric acid (isobutyric acid) derivative belonging to lipoprotein lipase activator class of drug. Results of clinical studies suggest that FEN can substantially reduce severe acute respiratory syndrome coronavirus 2. alpha and beta variant infection in human cell efficiently. This review article provides an in-depth examination of critical analytical methodologies used in the pharmaceutical analysis of FEN in pure forms, biological samples and pharmaceuticals. According to literature study reports several analytical techniques have been used for determination of FEN alone or in the combined dosage forms. Based on the literature, it was determined that high-performance liquid chromatography and UV/vis-spectrophotometry are the most widely used methods for FEN analysis. Sahoo et al. have developed the best HPLC method in bulk and pharmaceutical dosage form with the retention time of 19.268 min using phosphate buffer (pH 3.0): acetonitrile in the ratio of 30:70 (% v/v) as mobile phase. The information presented here may provide a solid foundation for future research on FEN in the field of drug analysis.