5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design, synthesis, molecular docking and evaluation. Issue 16 (1st September 2018)

• Record Type: Journal Article
• Authors: Fesatidou, Maria; Zagaliotis, Panagiotis; Camoutsis, Charalampos; Petrou, Anthi; Eleftheriou, Phaedra; Tratrat, Christophe; Haroun, Micheline; Geronikaki, Athina; Ciric, Ana; Sokovic, Marina
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 16(2018)
• Page Start: 4664
• Page End: 4676
• Publication Date: 2018-09-01
• Subjects: Adamantan -- Thiadiazole -- Thiazolidinone -- Antibacterial -- Antifungal -- Docking -- MurB -- MurA -- CYP51 -- Dihydrofolate reductase; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.08.004
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Seventeen novel 2-{[5-(adamantan-1-yl)-1, 3, 4-thiadiazol-2-yl]-imino}-5-arylidene-1, 3-thiazolidin-4-ones were designed, synthesized and evaluated for antimicrobial activity. All compounds were potent antimicrobial agents. According to molecular docking studies, inhibition of MurB and CYP 51 may be involved in the mechanism of antibacterial and antifungal activities of most of the compounds. Highlights: Novel adamantanyl thiadiazolyl thiazolidinones with antimicrobial activity. Molecular docking studies on E. coli MurB and MurA enzymes. Docking studies on dihydrofolate reductase and CYP51 enzymes of C. albicans. Abstract: 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.