New synergistic benzoquinone scaffolds as inhibitors of mycobacterial cytochrome bc1 complex to treat multi-drug resistant tuberculosis.

Through a comprehensive molecular docking study, a unique series of naphthoquinones clubbed azetidinone scaffolds was arrived with promising binding affinity to Mycobacterial Cytbc1 complex, a drug target chosen to kill multi-drug resistant Mycobacterium tuberculosis (MDR-Mtb). Five compounds from series-2, 2a, 2c, 2g, 2h, and 2j, showcased significant in vitro anti-tubercular activities against Mtb HRv and MDR clinical isolates. Further, synergistic studies of these compounds in combination with INH and RIF revealed a potent bactericidal effect of compound 2a at concentration of 0.

Physicochemical, Interaction & Topological Descriptors vs. hMAO-A Inhibition of Aplysinopsin Analogs: A Boulevard to the Discovery of Semi-synthetic Antidepression Agents.

Background: Depression, a neurological disorder, is globally the 4th leading cause of chronic disabilities in human beings.

Objective: This study aimed to model a 2D-QSAR equation that can facilitate the researchers to design better aplysinopsin analogs with potent hMAO-A inhibition.

Methods: Aplysinopsin analogs dataset were subjected to ADME assessment for drug-likeness suitability using StarDrop software before modeled equation.

Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl)arylamine derivatives as potential antitubercular agents.

A new series of novel triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20-40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20-40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus.

Design, synthesis, in silico and in vitro evaluation of novel diphenyl ether derivatives as potential antitubercular agents.

Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the fatty acid synthesis cycle of genus Mycobacterium. To select and validate a protein crystal structure of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis for designing inhibitors using molecular modelling, a cross-docking and correlation study was performed. A series of novel 1-(3-(3-hydroxy-4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) ethan-1-ones were synthesized from this model and screened for their antitubercular activity against M.

Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents.

A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored.

QSAR model for predicting the fungicidal action of 1,2,4-triazole derivatives against Candida albicans.

QSAR analysis of a series of previously synthesised 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols(TDFPP) as analogues of fluconazole were tested for growth inhibitory activity against Candida albicans using computer assisted multiple regression analysis. This was in order to explore the selectivity requirements for fungicidal activity against C. albicans among these congeners.