Antimicrobial and cytotoxic activities of thiazolo[4,5-b]pyridine derivatives

Abstract

Aim. The screening of antimicrobial and cytotoxic activities of thiazolo[4,5- b ]pyridine derivatives was accomplished. Methods. The antibacterial and antifungal activities of synthesized thiazolopyridines were evaluated in vitro with the agar diffusion and broth microdilution methods using clinical and reference strains of Gram-positive, Gram-negative bacteria and yeasts. The structure-antibacterial/antifungal activity relationships of the screened compounds were established. The target compounds were screened for their cytotoxicity effects on HaCaT and HEK293 cells using MTT assay. Results. The highest antimicrobial activity was observed for compound V 2-oxo-7-thiophen-2-yl-2,3-dihydrothiazolo[4,5- b ]pyridine-5-carboxylic acid with minimal inhibitory concentration (MIC) 12.5 μg/mL against Candida albicans . At the same time, the synthesized compounds were explored in the interaction with amoxicillin against multidrug resistant clinical isolates of ESβL + Klebsiella pneumonie and Staphylococcus haemolyticus (MRSH). The best synergistic activity with amoxicillin was exhibited by compound VI. HaCaT human keratinocytes and HEK293 human embryonic kidney cells demonstrated resistance to the thiazolopyridine derivatives treatment and did not reach the IC 50 value up to 100 µM. Conclusions. The tested thiazolopyridines constitute an interesting background for further development of new chemotherapeutic agents.