Discovery of oxazoline-triazole based hybrid molecules as DNA gyrase inhibitors: A new class of potential Anti-tubercular agents

Abstract

A library of novel oxazoline-triazole hybrid analogues (6a-6 g and 7a-7 m)was designed using a molecular hybridization approach and synthesized from commercially available ethyl 2/3/4-hydroxybenzoate. The synthesized compounds were characterized by modern art instrumentation, including IR and NMR (1H, 13C). All the final compounds were evaluated for their in-vitro antibacterial (S. aureus, B. subtilis, E. coli and P. aeruginosa), antifungal (C. neoformans, C. albicans and A. niger) and anti-tubercular (Mycobacterium tuberculosis H37Rv, MDR and XDR strains) activities. Among the series, compound 7a-7i exhibited excellent activity (MIC = 1.6 µM) against H37Rv strain of M.tuberculosis. However, antibacterial screening data (in vitro) revealed a moderate inhibition for 6e-6 g and 7f-7 h against gram-positive bacteria (Bacillus subtilis) and 7a-7i against gram-negative bacteria with a MIC value of 25 µg/ml. While moderate activity was observed against fungal (C. neoformns and C. albicans) strains with MIC value of 25–200 µg/mL. Additionally, five compounds (7a, 7d-7f and 7 h) were further evaluated for their in vitro inhibitory activity against E-coli DNA gyrase. These compounds displayed significant inhibitory activity against the DNA gyrase enzyme with an IC50 value of 0.08 – 0.5 µM.