DESIGN, SYNTHESIS, IN SILICO STUDY AND PRELIMINARY PHARMACOLOGICAL ASSESSMENT OF NEW GATIFLOXACIN ANALOGUES HAVING THIAZOLE NUCLEUS
ABSTRACT : Series of gatifloxacin derivatives (IVa-IVd) were synthesized by incorporation of thiazole ring (Which has antibacterial activity) and some of its derivatives into a secondary amine of piperazine ring at C-7 position of gatifloxacin nucleus, in order to increase bulkiness at this position by that reduce the affinity toward the efflux pump of bacterial cells, leading to reduction in bacterial resistance. By using FT-IR spectroscopy, 1H-NMR spectral and some of the physicochemical properties, the synthesized compounds were confirmed and characterized for their chemical structures. In-vitro study was performed to evaluate the antibacterial effect of all synthesized compounds and was revaluated by using agar- well diffusion method (AWD). The antibacterial study was shown a topmost inhibition zone for the compounds IVa and IVb against Staphylococcus aureus and the lowest inhibition zone for the two compounds IVc and IVd against E. coli. In silico study was performed using Molecular Operating Environment program and showed that all synthesized compounds were give affinity toward topoisomerase enzyme and these studies were compatible with the in vitro studies, as the compound IVb give the highest S score value.