Synthesis and antibacterial evaluation of a novel library of 2-(thiazol-5-yl)-1,3,4-oxadiazole derivatives against methicillin-resistant Staphylococcus aureus (MRSA).

Abstract

Replacement of the n-butylphenyl moiety in the lipophilic part of the previously reported arylthiazole antibiotics with naphthyl ring amended its activity against vancomycin resistant strains of Staphylococcus aureus. Incorporation of the CN linker connecting the nitrogenous head with thiazole within an oxadiazole ring provided orally available analogs with relatively long half-life. In this article, a set of new twenty-three derivatives of 2-(thiazol-5-yl)-1,3,4-oxadiazole was synthesized combining both structural modifications in one new scaffold with the objectives of enhancing both the pharmacokinetic profile and antibacterial activities vs. malicious microbes. Among the synthesized new compounds, five derivatives showed promising activity with MIC values ranging from 1.95 to 3.90 μg/mL. The guanidinyl-containing naphthylthiazole and N-methylpiperazinyl derivatives (25 &29) were found equipotent as vancomycin against MRSA (2658 RCMB). The other three derivatives (23, 24 and 26) revealed 50% of vancomycin activity.