Author(s):
G. Yuvaraja, R. Naveen Kumar, S. Divya, N. Renu
Email(s):
naveenkarthick55@gmail.com
DOI:
10.52711/0974-360X.2026.00500 
Address:
G. Yuvaraja, R. Naveen Kumar*, S. Divya, N. Renu
Department of Pharmaceutical Chemistry, PSV College of Pharmaceutical Science and Research, Krishnagiri – 635 108, Tamil Nadu, India.
*Corresponding Author
Published In:
Volume - 19,
Issue - 8,
Year - 2026
ABSTRACT:
Leprosy still poses a substantial public health burden and ongoing transmission as well as the emergence of rifampicin-resistance presents new problems for current multidrug treatment modalities. Herein, an advanced computational methodology which comprise of protein homology modeling, ADMET profiling and molecular docking was studied to identify the benzimidazole derivatives which target the beta subunit of DNA-dependent RNA polymerase of mycobacterium leprae. A high identity three-dimensional-structure of target enzyme was modelled by the homology modeling with the template A1KGE7 from AlphaFold and validated. Eight benzimidazole derivatives based on 2-(((1H-benzo[d]imidazol-2-yl) methyl) thio)-5-(4-(R) phenyl)-1H-benzo[d]imidazole template were rationally designed, analysed with respect to the PK and toxicity aspects, guided by Lipinski rule, and assessed for their participating in ADMET properties. Molecular docking by Autodock demonstrated better binding affinities for compounds 7,8 and 3 being -10.2, -9.8, -9.5 kcal/mol respectively as compared to reference drugs Rifampicin and Clofazimine whose binding affinities were calculated to be 8.4- and -9.2kcal/mol. Interaction studies were recognized significant conventional hydrogen bond, Pi-cation, halogen and hydrophobic interaction for improved binding specificity. SAR studies showed that electron donating and aromatic groups at selective positions to improve the ligand binding and prevent steric bulk. These results suggested that benzimidazole derivatives are potential lead compounds against rifampicin-resistant leprosy. This study paves way for biochemical validation and rational design optimization aimed these compounds toward clinical development.
Cite this article:
G. Yuvaraja, R. Naveen Kumar, S. Divya, N. Renu. In Silico Evaluation of Benzimidazole derivatives as Potent inhibitors Against Rifampicin-Resistant Mycobacterium leprae: Targeting DNA-Dependent RNA Polymerase. Research Journal of Pharmacy and Technology. 2026;19(8):3531-8. doi: 10.52711/0974-360X.2026.00500
Cite(Electronic):
G. Yuvaraja, R. Naveen Kumar, S. Divya, N. Renu. In Silico Evaluation of Benzimidazole derivatives as Potent inhibitors Against Rifampicin-Resistant Mycobacterium leprae: Targeting DNA-Dependent RNA Polymerase. Research Journal of Pharmacy and Technology. 2026;19(8):3531-8. doi: 10.52711/0974-360X.2026.00500 Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-8-17
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