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Research Article Volume 13 Issue 3
Rational design and pharmacological profiling of benzimidazole-based compounds via in silico and in vitro approaches
Avantika G Parit, Sandeep R Kane, Shrinivas K Mohite, Somkant V Jawarkar, Pallavi B Sutar
Received: July 28, 2025 | Published: August 12, 2025
Citation: Parit AG, Kane SR, Mohite SK, et al. Rational design and pharmacological profiling of benzimidazole-based compounds via in silico and in vitro approaches. J Microbiol Exp. 2025;13(3):68-82. DOI: 10.15406/jmen.2025.13.00435
Abstract
Benzimidazole derivatives, particularly those modified at the N-1 and C-2 positions, have shown strong potential as anticancer agents. This thesis focuses on the design, synthesis, and computational evaluation of novel N-substituted 2-substituted benzimidazole compounds aimed at enhancing anticancer activity. Guided by QSAR analysis, functional groups were strategically introduced, and compounds were synthesized using both conventional and microwave-assisted methods, with the latter demonstrating superior efficiency most notably for compound A3, which yielded 96%. Structural confirmation of the synthesized compounds was carried out using TLC, IR, NMR, and mass spectroscopy. Among all derivatives, A3 emerged as the most promising, showing strong binding affinity to the EGFR kinase domain (PDB: 1XKK) in docking studies, 86% inhibition in the Trypan Blue assay, and an IC₅₀ of 23.47µM in the MTT assay, closely comparable to the standard drug 5-fluorouracil. Active site identification via pdCSM, GeneCard, and PathCard provided insights into potential mechanisms of action, while ADMET and toxicity profiling predicted high bioavailability , low toxicity , and favourable drug-likeness. QSAR modelling further supported these findings, with a high correlation coefficient (R² = 0.972) identifying A3 as the top candidate. Overall, this integrated approach combining synthesis, computational evaluation, and pharmacological screening highlights compound A3 as a strong lead for further development of effective and safer benzimidazole-based anticancer therapies.
Keywords: Benzimidazole, microwave assisted synthesis, molecular docking study, in-silico ADMET analysis, toxicity study, anticancer activity, antibacterial activity, antioxidant activity, QSAR, IC50, RMSD, MTT, trypan blue assay
©2025 Parit, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.