Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study
| Autor: | Shailee V. Tiwari, Aniket P. Sarkate, M. Vázquez-Tato, Kshipra S. Karnik, Julio A. Seijas, Anna Pratima Nikalje |
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| Přispěvatelé: | Universidade de Santiago de Compostela. Departamento de Química Orgánica |
| Rok vydání: | 2018 |
| Předmět: |
Cytotoxicity
Pharmaceutical Science Ionic Liquids Ionic liquid Carbohydrazide 01 natural sciences Analytical Chemistry HeLa chemistry.chemical_compound antibacterial activity Drug Discovery Antifungal activity biology Molecular Structure Anti-Bacterial Agents Molecular Docking Simulation Chemistry (miscellaneous) Molecular docking In vivo acute oral toxicity Chromone Molecular Medicine cytotoxicity Antibacterial activity medicine.drug Pyrimidine Antineoplastic Agents Microbial Sensitivity Tests Article ionic liquid antifungal activity molecular docking in vivo acute oral toxicity lcsh:QD241-441 Structure-Activity Relationship lcsh:Organic chemistry medicine Humans Physical and Theoretical Chemistry Mode of action 010405 organic chemistry Organic Chemistry biology.organism_classification Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Pyrimidines chemistry Docking (molecular) Chromones Miconazole Drug Screening Assays Antitumor HeLa Cells |
| Zdroj: | Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry Molecules, Vol 23, Iss 2, p 440 (2018) Molecules; Volume 23; Issue 2; Pages: 440 Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname |
| ISSN: | 1420-3049 |
| Popis: | Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et3NH][HSO4])-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 4(a–f) and 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a–f). All the synthesized derivatives 4(a–f) and 6(a–f) were evaluated for their in vitro antifungal and antibacterial activity, by method recommended by National Committee for Clinical Laboratory Standards (NCCLS). The compound 6c bearing a fluoro group on the chromone ring and oxygen and a hydrazino group (–NHNH2) on the pyrimidine ring, was found to be the most potent antibacterial compound amongst the synthesized derivatives. The compound 6f bearing a methoxy group (–OCH3) on the chromone ring and sulphur group on the pyrimidine ring, was found to exhibit equipotent antifungal activity when compared with the standard drug miconazole. A d-alanine-d-alanine ligase (DdlB) enzyme assay study and an ergosterol extraction and quantitation assay study were performed to predict the mode of action of the synthesized compounds. A molecular docking study was performed to predict the binding interactions with receptors and mode of action of the synthesized derivatives. Further, analysis of the ADMET parameters for the synthesized compounds has shown that these compounds have good oral drug-like properties and can be developed as oral drug candidates. To establish the antimicrobial selectivity and safety, the most active compounds 6c and 6f were further tested for cytotoxicity against the 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 6c and 6f and the results indicated that the compounds are non-toxic in nature. SI |
| Databáze: | OpenAIRE |
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