Molecular Docking Studies of Novel Benzimidazole Analogs as HIV-1-RT Inhibitors with Broad Spectrum Chemotherapeutic Properties

The urgent need for novel HIV-1-RT inhibitors with broad spectrum chemotherapeutic properties has provided an impetus for understanding the structural requisites of HIV-1-RT inhibitors at the molecular level. Toward this objective, binding mode analysis of 113 benzimidazole analogs was performed. First, molecular docking studies were performed on novel benzimidazoles by Glide program in the active site of four different enzymes namely HIV-1 reverse transcriptase (PDB code 1RT2), peptide deformylase (PDB code 1G2A), Mycobacterium tuberculosis-CYP51 (PDB code 1EA1) and Candida albicans (CACYP51) (PDB code chimeric-1EA1) to study the binding mode of these analogs. Second, statistical analysis was performed on the basis of the docking scores obtained by docking. Results generated from this study indicate that most of the compounds dock into the active site of different enzymes such as 1RT2, 1G2A, 1EA1 and chimeric-1EA1 enzymes showing good docking scores comparable to the standard compounds. The docking analysis of the highest active compound 35 revealed significant interaction along with H-bond interactions into the active site amino acid residues of 1RT2, 1G2A, 1EA1 and chimeric1EA1.