Molecular Docking, ADME Study, Synthesis And Characterization Of Some 1,2,3-Triazole Derivatives Of 4-(1H-Benzimidazol-2-Yl) Aniline

Abstract

A number of novel 1,2,3-triazole-based benzimidazole derivatives (4a-c) have been created using the Cu-catalyzed cycloaddition of alkyne and azide reaction (CuAAC). Compound 1 was synthesized from treatment of p-amino benzoic acid with o-phenylenediamine, it was converted into azide (compound 3) by treatment compound 2 (amide that prepare from reaction of compound 1 with chloroacetyl chloride) with sodium azide. Compound 3 was converted into 1,2,3-triazole derivatives (4a-c) by treatment with acetylene derivatives. The intermediates and final compounds molecular structures are characterized and confirmed by FTIR, ¹H-NMR and Mass spectra. In this present research, some benzimidazole derivatives bearing 1,2,3-triazole moiety were subjected to molecular docking to create safe and efficient molecules. To test each derivative's ability to bind to the enzyme's active site, it was docked into the active sites of Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes bacteria that originate from the crystal structure form of the enzymes in complex with anti-bacterial drug, Trimethoprim ( reference drug), whose PDB ID were 1NNI, 3G7E, 4HL2, 2W9S, and 4RKX. Swiss ADME was used to undertake ADME study to determine the topological polar surface area, bioavailability, and drug-likeness of the synthesized molecule. The outcome demonstrated that the investigated chemicals were orally absorbed and adhered to the Lipinski rule.