Novel transition metal complexes of 5-(2-phenyl-1H-benzo[d]imidazol-1-yl)quinolin-8-ol as active pharmacophore: Experimental and computational explorations

Abstract

l New ligand derived from benzimidazole and 5-chloro-8-hydroxy quinoline, and its tansition metal complexes have been synthesized. l Characterized by 1 H NMR, IR, mass spectroscopy, XRD, elemental analysis and DFT methods. l In vitro antimicrobial activity of ligand and its complexes were determined. l Molecular docking and ADMET predictions of metal complexes shown as promising lead-like characters. A novel 5-(2-phenyl-1H-benzo[d]imidazol-1-yl)quinolin-8-ol ligand (PBIQ) ligand was used to synthesize a series of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes. Elemental analysis, FTIR, 1H NMR, UV-Visible and mass spectra were utilized to characterize the newly synthesized ligand and its transition metal complexes. The antimicrobial activity of the ligand and complexes were evaluated against four bacterial and one fungal strain using the minimum inhibitory concentration method (MIC). The minimum inhibition concentration observed was compared against the standard antibiotic rifampicin and the antifungal drug fluconazole. The studies revealed that Cu(II) and Zn(II) complexes are more effective against tested bacterial and fungal strains compared to the ligand and other complexes. Molecular docking techniques revealed that the Cu(II)-PBIQ complex associated with the target protein (PDB ID: 4HL2 ) had a greater binding affinity with π-σ, π-alkyl and hydrophobic interactions. Density function theory (DFT) calculations were applied to evaluate the optimized geometrical structures and to calculate the global reactivity descriptors of the more active Cu(II) and Zn(II) complexes. Besides, the in-silico pharmacokinetics showed that all the examined metal complexes compounds obeyed Lipinski's Rule of five with one violation.