Identification of Potential Anticancer Phytochemicals of <i>Piper chaba</i> by Comprehensive Molecular Docking, Molecular Dynamics Simulation and In‐Vitro Studies

Human colon cancer and prostate cancer are the most common malignancy globally. Despite the availability of many treatments, resistance to traditional medicines, such as chemotherapy and radiotherapy, remains a severe obstacle in cancer treatment. Hence, searching for new therapeutic options is of utmost priority. The present investigation evaluates the in-silico and in-vitro anticancer potential of phytochemicals of Piper chaba. The cytotoxicity results demonstrated that the plant extract exhibited significant anticancer activity, with IC₅₀ values of 12.66 ± 0.25 µg/mL for HCT-116 and 19.49 ± 0.37 µg/mL for DU-145. Molecular docking and molecular dynamics simulations were performed to explore the interaction of potential drug targets with the phytochemicals. Subsequently, pharmacokinetic parameters calculations were performed to evaluate the drug-likeness. Piperine exhibits the highest binding affinity for vascular endothelial growth factor receptor-2 (VEGFR2) protein with a docking score of -9.71 kcal/mol. Sylvatine had a greater binding affinity for human epidermal growth factor receptor 3 (HER3) protein than the other phytochemicals. Isopiperine, chabamide, Piperlonguminine, Santamarine and Versalide only exhibited ligand activity for human IKK beta protein (inhibitor of kappa B kinase). Additionally, a principal component analysis was performed to strengthen the investigation's scope. These proposed phytochemicals are reported to possess potential VEGFR2, HER2 and human IKK beta inhibition. The best phytochemical hits have excellent binding affinity and hold a massive anticancer potential, opening up new avenues for prospective future investigations in cancer treatment.