Computational Investigation of Polo-like Kinase 1 (plk1): Inhibitive Potential of Benzimidazole-Carbonamide Derivatives for Cancer Treatment

Cancer is the second most lethal disease worldwide after cardiovascular disease. Discovering and developing new drugs and repurposing existing drugs to curb this disease have gathered interest from researchers globally. In this work, computer-aided approaches via density functional theory (DFT), molecular docking, and pharmacokinetics were adopted for the evaluation of anti-breast cancer activity of 2-({4-[(1H-Benzimidazol-2-yl)sulfanyl]phenyl}methylidene)hydrazine-1-carbothioamide and its modified derivatives. In the result, the BMHCd showed the lowest bang gap energy, highest enthalpy change, and highest Gibb’s free energy indicating the most reactive among the compounds. Also, molecular docking showed that all the compounds have stable interactions and higher binding energy, with BMHCf showing the highest (-8.469 kcal/mol). Furthermore, all the compounds satisfy the Lipinski rule of five and are therefore, good therapeutic candidates for the treatment of human cancer.