Computational analysis synthesis and anticancer potential of 2 substituted benzimidazole derivatives

Abstract

newline Three different series of benzimidazole compounds were docked against both the estrogen receptor alpha (ERand#945;) and cyclin dependent kinase (CDK-8). The docking results revealed that the benzimidazole thiazolidinone derivatives fused with pyrazole showed promising results. The results also indicated that the interaction with estrogen receptor alpha were more significant than with cyclin dependent kinase (CDK-8). This suggests that the benzimidazole compounds, particularly the pyrazole containing series, have a stronger binding affinity or more favourable interactions with estrogen receptor alpha. To further validate the docking results and assess the stability of the designed leads over time, molecular dynamics (MD) simulations were executed. Molecular dynamic simulations provide insights into the dynamic behavior and stability of the ligand-receptor complex within the macromolecular cavity over a period of time. The fact that the docking results with estrogen receptor alpha were further confirmed by molecular dynamics simulations adds credibility to the findings. Stability over time is crucial for the development of effective therapeutics, and Molecular Dynamics (MD) simulations are indeed a valuable tool in assessing the robustness and dynamics of ligand-receptor interactions. Based on the cumulative results, it is proposed that benzimidazole nucleus in combination with pyrazole can serve as a promising pharmacophore. This thesis explores the anticancer potential of some potent novel designed benzimidazole thiazolidinone derivatives fused with five-membered heteroatom containing ring (pyrazole) (XII-XXVI) formed by the reaction of 1-(1H-benzimidazol-2-yl)-2-hydrazinylethan-1-one with substituted -pyrazole -4- carbaldehyde, crude product so obtained was treated with thioglycolic acid in dioxane to give target derivatives. By combining the information obtained from different spectroscopic techniques (1H-NMR, 13C-NMR and IR) in addition to mass spectrometry.