In-silico investigation and drug likeliness studies of benzimidazole congeners: The new face of innovation

Abstract

BackgroundThe primary driving force behind the development of several small molecules for the treatment of tuberculosis is multi-drug resistance. A new fluorinated heterocyclic benzimidazole derivative gives extensive pharmacological activity against the FtsZ protein. FtsZ is a new validated target for tuberculosis drug design. It is a cell division filament protein present in Mycobacterium tuberculosis and other bacteria. MethodsLigand preparation- The ligand molecules were selected from the previously published paper and analyzed for reliability with the FtsZ protein. The 3D structure of the ligand was prepared using Chem-Draw Pro (version 12.0). Protein preparation- The PDB format FtsZ protein was downloaded from RCSB (https://www.rcsb.org/). The FtsZ protein of PDBID 2q1y was taken for the docking studies. The binding pocket was determined using the Castp server (http://sts.bioe.uic.edu/castp/index.html?201l). Thereafter, the in-silico docking was performed using PyRx 1.0 software. ResultThe docking result explains the importance of benzimidazole derivatives as potential FtsZ inhibitors. This study was focused on the in-silico development of new inhibitors and their chances to develop the candidate for oral delivery. The binding free energy, ADMET properties, and druglikeness characteristic of benzimidazole derivatives make them a perfect candidate for FtsZ inhibitors. Compound A-21 and A-20 had the best binding energy of −9.0 kcal/mol and −8.9 kcal/mol respectively. Molecular docking study revealed that Asn41, Thr42, Gly69, and Ala70 are required for conventional hydrogen bonding. The majority of the compounds (A-1, A-23 to A-32) are substrates for P-gp, which implies that their concentration inside the cell remain low due to P-efflux mechanism. ConclusionCompound A-20 formed five H-bond with target proteins (Gln30, Thr200, Gly226, Asp296, Val305). Almost all the molecules fulfil the criteria of drug likeliness. From this result, it can be concluded that benzimidazole derivatives can be developed as a new anti-Tb agent.