Synthesis, biological evaluation and molecular docking studies of thiazolo[4,5‐ b ]pyridin‐5‐ones as antimicrobial agents

Abstract

Herein we report the design and synthesis of thiazolo[4,5-b]pyridin-5-ones and evaluation of their antimicrobial activity. The design was based on a molecular hybridization approach. Evaluation of their antibacterial activity revealed that these compounds generally showed moderate antibacterial activity. The best activity was achieved for compound 4p with MIC/MBC in the range of 0.12-0.47 and 0.23-0.94 mg mL(-1) respectively. Three compounds (4g, 4n, and 4p) were tested against three resistant strains, namely MRSA, p.aeruginosa, and E.coli, showing higher inhibition potential than the reference drug ampicillin. These three compounds also were tested for their ability to inhibit biofilm formation, with two of them showing better activity than streptomycin in a concentration of MIC (4p) and ampicillin in both concentrations (MIC and 0.5 MIC). As far as antifungal activity is concerned, the best activity was observed for compound 4i with MIC at 0.12-0.47 mg mL(-1) and MFC at 0.23-0.94 mg m(-1). According to docking studies, the predicted inhibition of E.coli MurB enzyme is probably a putative mechanism of the antibacterial activity of these compounds, while inhibition of 14a-lanosterol demethylase is probably the mechanism of their antifungal activity.