Chemical Synthesis and Hemi-synthesis of novel benzimidazoles derivatives using microwave-assisted process: chemical characterization, bioactivities, and molecular docking study

Benzimidazoles derivatives represent a class of heterocyclic compounds that exhibit a wide range of pharmaceutical properties. The present study aimed to investigate the in-vitro antioxidant and antimicrobial activities of newly synthesized benzimidazoles derivatives. Compound 1b, (2-(1H-1,3-benzodiazol-2-yl) phenol) was synthesized by reacting o-phenylenediamine (OPA) with chemical salicylaldehyde, while compound 2b, (2-(1E)-2-phenylethenyl-1H-1,3-benzodiazole) and 3b (2-(1E)-2,6-dimethylhepta-1,5-dien-1-yl-1H-1,3-benzodiazole) were obtained through hemi-synthesis process of respectively the cinnamon (cinnamaldehyde, 85%), and lemongrass (citral, 49,5%) essential oils previously characterized by GCMS. Compounds 4b, 2-phenyl-1H-benzimidazole, 5b, (2-(1H-benzimidazol-2-yl)phenol), and 6b, (5-(1H-benzimidazol-2-yl)benzene-1,2,3-triol) were synthesized with click chemistry method by reacting the OPA with Benzoic acid, salicylic acid, and gallic acid directly in ethanol under microwave irradiation. The structure/purity of the synthesized compounds was clarified by spectroscopy ATR-FTIR and NMR 1H. Compounds 1b-6b were screened for their antioxidant activity by using four complementary in vitro assays: DPPH scavenging activity, ferric ion reducing power, β-carotene bleaching inhibition, and TBARS formation inhibition. All the tested compounds showed antioxidant potential with different performances. Antimicrobial activity was investigated against ATCC strains (three Gram- bacteria: Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa, one Gram+ bacteria: Staphylococcus aureus, and one yeast stain Candida albicans) through the determination of MIC and MBC by using the microdilution method and rapid colorimetric test of p-iodonitrotetrazolium chloride (INT). Compound 6b exhibited the highest potential especially against S. aureus (CMI = 0,156 mg.mL-1) followed S. typhi and C. albicans (CMI = 0.3125 mg.mL-1), then E.coli and and P. aeruginosa by compound 1b also showed a great potential against S. aureus et C. albicans (CMI ˂0.3125 mg/mL), followed by E.coli and S. typhi (CMI = 0.3125mg/mL), and P. aeruginosa (CMI = 0.625 mg/mL). A further molecular docking was proceeded using Autodock vina software on s. aureus thymidylate kinase TMK-protein to highlight the structure-activity relationship of the potent molecules.