Synthesis, characterization, and biological investigations of potentially bioactive heterocyclic compounds containing benzimidazole nucleus

Abstract

Six benzimidazole derivatives have been synthesized and characterized using spectroscopic techniques such as IR, 1H NMR, 13C NMR, and mass spectrometry. The computational calculations and geometrical optimization of newly synthesized benzimidazole derivatives were investigated using Gaussian software in conjunction with the Density functional theory (DFT)/B3LYP method with a 6–311++G(d,p) basis set at gaseous phase. In addition, the quantum chemical parameters of the compounds were evaluated to comprehend the structural activity concept. The synthesized compounds were tested for cytotoxicity using the MTT assay and antioxidant activity using the DPPH scavenging activity and the Ferrous-Ion Chelating Assay. All the compounds tested showed antioxidant, antidibetic, cytotoxic potential, with compounds 4c and 4f being the best of all derivatives. The agar diffusion method was used to conduct antimicrobial assays for bacteria and fungi. Even though none of the compounds were found to be effective against fungi isolates and some had a poor anti-bacterial effect, compound 4f had a significantly higher antibacterial effect against all bacteria strains (S. aureus, Bacillus cereus, E. coli, and Acetobacter sp.). Furthermore, in vitro anticancer properties of synthesized compounds were validated using in silico molecular docking simulation studies. Compound 4c had the highest binding affinity of all the ligands, with a binding energy of −5.9 Kcal/mol and three hydrogen bonds.