Synthesis, Antimicrobial Activity and Molecular Docking Studies of 1,3‐Thiazole Derivatives Incorporating Adamantanyl Moiety

Abstract

Synthesis, characterization and investigation of antimicrobial activity of 11 novel adamantanyl‐thiazoles are presented. Their structures were determined using 1H and 13C NMR, EI(+)‐MS, HRMS, and elemental analyses. Among the derivatives, compound 3c showed very strong activity, especially against Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 with minimal inhibitory concentration (MIC) values ranging from 1.95 to 7.81 µg/ml. Compounds 3a and 3b showed good antifungal activity. Among the examined compounds, the widest spectrum of antibacterial activity possessed 3f that showed good activity, especially against Staphylococcus epidermidis ATCC 12228, Micrococcus luteus ATCC 10240, Bacillus subtilis ATCC 6633 with MIC values ranging from 31.25 to 62.5 µg/ml. Molecular docking studies of all compounds on the active sites of microbial enzymes indicated possible targets sterol 14α‐demethylase, secreted aspartic proteinase (SAP), N‐myristoyltransferase (NMT), and topoisomerase II. Thiazoles 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k showed more favorable affinity to SAP and NMT than the native ligand.