Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study

Abstract

The work reports the synthesis under solvent-free condition using the ionic liquid [Et3NH][HSO4] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2-onederivatives 4a–o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their in vitro antifungal and antibacterial activity. The compound 4k bearing 4-hydroxy-3-ethoxy group on the phenyl ring was found to be the most active antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring was found to be the most active antibacterial agent. The mode of action of the most promising antifungal compound 4k was established by an ergosterol extraction and quantitation assay. From the assay it was found that 4k acts by inhibition of ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which suggests that the tested compounds inhibit the synthesis of this enzyme. The synthesized compounds were analyzed for in silico ADMET properties to establish oral drug like behavior and showed satisfactory results. To establish the antimicrobial selectivity and safety, the most active compounds 4e and 4k were further tested for cytotoxicity against human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 4e and 4k and results indicated that the compounds are non-toxic.

Peel Extract Associated Oxidative Green Dakin Synthesis of Some Phenols Using Aqueous Banana Extract Catalyst

“…In the continuation of our previous work [11][12][13][14][15][16][17][18][19][20][21][22][23] , it was confirmed that until now none of the methods had used such a mild and green catalyst and solvents for Dakin oxidation. The designed method is suitable for the conversion of substituted benzaldehydes to its consequent substituted phenols.…”

Auto QSAR‐ A Fast Approach for Creation and Application of QSAR Models through Automation

“…[a] Molecular weight of the molecule, [b] Predicted octanol/water partition co‐efficient log P (acceptable range: −2.0 to 6.5) ,. [c] Predicted aqueous solubility; S in mol/L (acceptable range: −6.5 to 0.5).…”

Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties

“…All the novel compounds from both series, the carboxamides 3a – m and Schiff base carbohydrazides 5a – l , were screened for in vitro antibacterial activity against Pseudomonas aeruginosa, Escherichia coli , Klebsiella pneumoniae , Salmonella typhi and Bacillus subtilis . Methods, as recommended by the National Committee for Clinical Laboratory Standards (NCCLS), were used to determine the corresponding minimum inhibitory concentration (MIC) values [ 27 , 28 , 29 , 30 ]. Stock solutions were prepared in dimethyl sulfoxide (DMSO) and DMSO alone served as solvent control.…”