Synthesis of analogues of N-4-piperazinyl ciprofloxacin derivatives 4a-j.

Synthesis of analogues of N-4-piperazinyl ciprofloxacin derivatives 4a-j.</p

Influence of ciprofloxacin derivatives 4a-j on the activity of protease.

Influence of ciprofloxacin derivatives 4a-j on the activity of protease.</p

Determination of % inhibition of protease activity (μ/mL) 4a-j.

Determination of % inhibition of protease activity (μ/mL) 4a-j.</p

Ligands interaction profile within the active site of protease.

Two dimensional (2D) illustration of ciprofloxacin (A) and compound 4a (B) interacting with active site residues.</p

Parameters for induced fit docking and Prime/MM-GBSA simulation of test ligands at binding pocket of protease.

Parameters for induced fit docking and Prime/MM-GBSA simulation of test ligands at binding pocket of protease.</p

Synthesized <i>N</i>-4-piperazinyl ciprofloxacin derivatives 4a-j [17].

Synthesized N-4-piperazinyl ciprofloxacin derivatives 4a-j [17].</p

Determination of half-life of ciprofloxacin derivatives 4a-j.

Determination of half-life of ciprofloxacin derivatives 4a-j.</p

Structure of nalidixic acid.

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 , and non-competitive inhibition with 0.1±0.00μM Ki. 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 ΔGbind.</div

Structures of compounds 4a and 4i active against <i>Escherichia coli</i>.

Structures of compounds 4a and 4i active against Escherichia coli.</p

Zone of inhibition values (millimeters) of compounds 4a-j.

Zone of inhibition values (millimeters) of compounds 4a-j.</p