Discovery of novel 1,3,5-triazines as potent antibacterial agent against urinary tract infection-causing clinical isolates of Escherichia coli via inhibition of DNA Gyrase.

A novel series of 1,3,5-triazine-phenylthiazole-pyrazole derivatives were synthesized and subsequently tested for Escherichia coli DNA Gyrase inhibitory activity where they showed excellent inhibitory activity. The top-three ranked DNA gyrase inhibitor (4e, 4g and 4h) were further subjected to antibacterial and anti-biofilm activity against clinical isolates of resistant E. coli strains obtained from Urinary Tract Infection (UTI) patients (CREC81, CREC106, CREC163). Compound 4h was identified as most potent antibacterial agent in the above study. The compound 4h was further evaluated in murine model of E. coli UTI in BALB/c mice infected by transurethral injection of CREC106 strain. Results of the study suggest that compound 4h reduces bacterial load of CREC106 in the treated mice and found approximately equipotent to Novobiocin as standard.