Molecular Design and In-Silico Analysis of Trisubstituted Benzimidazole Derivatives as Ftsz Inhibitor

Tuberculosis (TB) is the fastest spreading infectious disease and one of top ten diseases that kill millions people annually. The rapid spread a multidrug-resistant strain Mycobacterium tuberculosis leads to multidrug-resistance (MDR-TB), which very difficult treat. Filament temperature-sensitive protein ring-Z (Ftsz) could be best target inhibit bacterial cytokinesis. This research conducted predict antitubercular activity trisubstituted benzimidazole derivatives targeting FtsZ by an in-silico approach (molecular docking, pharmacokinetic parameter, drug likeliness, toxicity prediction, biological prediction). Amine aldehyde substitutions are used as primary scaffolds design 20 for molecular docking. AutoDock vina v.1.2.0 software was binding interaction between ligand receptor (FtsZ, PDB ID : 1RQ7). drug-likeliness properties ligands were predicted from SwissADMET ToxiM web servers, respectively. Compound A15 (2,3,5,6-tetrafluoro-N1-{6-fluoro-5-[4-(1H-imidazole-1-yl) phenoxy]-1H-1,3-benzodiazol-2-yl} benzene-1,4-diamine) showed energy (ΔG = −10.2 kcal/mol/) along with four hydrogen bond interactions (GLY107, PHE180, ASP 184). Similarly, compounds A19 A20 have score −9.8 kcal/mol, excellent parameters. It found all −8.0 kcal/mol) better than reference compound Moxifloxacin −7.7 kcal/mol). None violate Lipinski’s rule, but ligands’ slightly high (>0.8 score). reported amine-substituted substitution. Therefore, it concluded can candidate Ftsz inhibitors in-vitro animal study necessary validate these data.