RT Journal Article
T1 Facile synthesis of novel coumarin derivatives, antimicrobial analysis, enzyme assay, docking study, ADMET prediction and toxicity study
A1 Tiwari, Shailee V.
A1 Seijas Vázquez, Julio Antonio
A1 Vázquez Tato, María del Pilar
A1 Sarkate, Aniket
A1 Karnik, Kshipra S.
A1 Nikalje, Anna Pratima G.
K1 Ionic liquid
K1 Antifungal activity
K1 Antibacterial activity
K1 Molecular docking
K1 Cytotoxicity
K1 In vivo acute oral toxicity
AB 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.
PB MDPI
YR 2017
FD 2017
LK http://hdl.handle.net/10347/22679
UL http://hdl.handle.net/10347/22679
LA eng
NO Tiwari, S.V.; Seijas, J.A.; Vazquez-Tato, M.P.; Sarkate, A.P.; Karnik, K.S.; Nikalje, A.P.G. Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study. Molecules 2017, 22, 1172.
DS Minerva
RD 3 may 2026