Design, Development and Evaluation of N-Mannich Base Prodrugs of Norfloxacin For In Vitro Release Behavior and Antimicrobial Properties

Abstract

In this research work, prodrugs of norfloxacin with various benzothiazoles were synthesized and studied for hydrolytic studies at various physiological pH. The results indicated that all of the prodrugs exhibited more and faster hydrolysis mainly in phosphate buffer (pH 7.4) rather than in HCl buffer (pH 1.2). These prodrugs were characterized by FTIR, 1H NMR, mass spectroscopy and physical analysis. The synthesized prodrugs showed better partition coefficient as compared to parent compound, norfloxacin. All of the prodrugs were tested for antimicrobial activity against selected microbial strains. Among the synthesized prodrugs, M1 was found to exhibit significant antibacterial efficacy having MIC 6.25 µg/ml against S. aureus MTCC 96 and prodrug M6 depicted good antibacterial activity (MIC 6.25 µg/ml) against E. coli MTCC 443 when compared with norfloxacin (MIC 10 µg/ml). Prodrugs M2 and M4 showed comparable activity against E. coli MTCC 443 and P. aeruginosa MTCC 1688 respectively to standard drug norfloxacin. The antibacterial activity of prodrug M4 (MIC 25 µg/ml) was found to be better than ciprofloxacin (MIC 50 µg/ml) against S. pyogenus MTCC 442. Moreover, prodrugs M4 and M6 possessed better antifungal activities (MIC 250, 75 µg/ml respectively) against C. albicans MTCC 227 while M2 showed significant potency against A. niger MTCC 282 and A. clavatus MTCC 1323 (MIC 50 µg/ml) compared to standard drug nystatin (MIC 100 µg/ml).