Facile synthesis of novel coumarin derivatives, antimicrobial analysis, enzyme assay, docking study, ADMET prediction and toxicity study
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|Title:||Facile synthesis of novel coumarin derivatives, antimicrobial analysis, enzyme assay, docking study, ADMET prediction and toxicity study
|Author:||Tiwari, Shailee V.
Seijas Vázquez, Julio Antonio
Vázquez Tato, María del Pilar
Karnik, Kshipra S.
Nikalje, Anna Pratima G.
|Affiliation:||Universidade de Santiago de Compostela. Departamento de Química Orgánica
|Subject:||Ionic liquid | Antifungal activity | Antibacterial activity | Molecular docking | Cytotoxicity | In vivo acute oral toxicity ||
|Date of Issue:||2017
|Citation:||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.
|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.|
|Rights:||© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
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