5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design, synthesis, molecular docking and evaluation
| Autor: | Phaedra Eleftheriou, Athina Geronikaki, Marina Soković, Panagiotis Zagaliotis, Micheline Haroun, Charalampos Camoutsis, Ana Ćirić, Anthi Petrou, Christophe Tratrat, Maria Fesatidou |
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| Rok vydání: | 2018 |
| Předmět: |
Clinical Biochemistry
Dihydrofolate reductase Pharmaceutical Science Adamantane 01 natural sciences Biochemistry Docking Anti-Infective Agents Ampicillin Drug Discovery biology Chemistry Escherichia coli Proteins Antimicrobial 3. Good health Molecular Docking Simulation Thiazolidinone Molecular Medicine Thiazolidines Antibacterial activity medicine.drug Stereochemistry Bifonazole Microbial Sensitivity Tests CYP51 Gram-Positive Bacteria Adamantan Antifungal Fungal Proteins Structure-Activity Relationship Drug Resistance Bacterial Gram-Negative Bacteria Thiadiazoles MurA medicine Escherichia coli MurB Potency Molecular Biology Binding Sites 010405 organic chemistry Organic Chemistry biology.organism_classification 0104 chemical sciences Protein Structure Tertiary Antibacterial 010404 medicinal & biomolecular chemistry Thiadiazole Docking (molecular) Drug Design biology.protein Bacteria |
| Zdroj: | Bioorganic & Medicinal Chemistry |
| Popis: | In continuation of our efforts to develop new compounds with antimicrobial properties we describe design, synthesis, molecular docking study and evaluation of antimicrobial activity of seventeen novel 2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-arylidene-1,3-thiazolidin-4-ones. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. Twelve out of seventeen compounds were more potent than streptomycin and all compounds exhibited higher potency than ampicillin. Compounds were also tested against three resistant bacterial strains: MRSA, P. aeruginosa and E. coli. The best antibacterial potential against ATCC and resistant strains was observed for compound 8 (2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-(4-nitrobenzylidene)-1,3thiazolidin-4-one). The most sensitive bacterium appeared to be S. typhimirium, followed by B. cereus while L. monocitogenes and M. flavus were the most resistant. Compounds were also tested for their antifungal activity against eight fungal species. All compounds exhibited antifungal activity better than the reference drugs bifonazole and ketokonazole (3-115 times). It was found that compound 8 appeared again to be the most potent. Molecular docking studies on E. coli MurB, MurA as well as C. albicans CYP 51 and dihydrofolate reductase were used for the prediction of mechanism of antibacterial and antifungal activities confirming the experimental results. |
| Databáze: | OpenAIRE |
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