Protease inhibition, in vitro antibacterial and IFD/MM-GBSA studies of ciprofloxacin-based acetanilides

In this study, we have investigated ciprofloxacin-based acetanilides for their in-vitro inhibitory study against gram +ve, -ve bacteria and serine protease activity. The compounds 4e and 4g showed excellent antibacterial activity against Bacillus subtilis with a zone of inhibition (ZI) values of 40 +/- 0.9 mm, 37 +/- 1.4 mm and with MIC values of 4.0 +/- 0.78 mg/mL, 3.0 +/- 0.98 mg/ML respectively, while 4a and 4i were found most active against Escherichia coli, with ZI values 38 +/- 0.1 mm, 46 +/- 1.8 mm and with MIC values of 1.0 +/- 0.25 mg/mL, 1.0 +/- 0.23 mg/mL respectively. All derivatives (4a-j) significantly inhibited the catalytic activity of serine protease, while 4a exhibited a maximum (100%) inhibitory effect at 96 minutes having 22.50 minutes t1/2, and non-competitive inhibition with 0.1 +/- 0.00 mu M K-i. The IFD/MM-GBSA studies highlighted the binding mode of 4a for protease inhibition and indicated improved binding affinity with -107.62 kcal/mol of Delta G(bind).