Exploring the Potent Anticancer Activity of Novel Phytoconstituent Derived from Zanthoxylum Nitidum Using an In-Silico Approach

Background: Cancer is one of the serious health issues and the leading cause of mortality worldwide. Several studies have demonstrated that the overexpression of growth factors and receptors, the triggering of oncogenes, and the deactivation of tumor suppressor genes are the main causes of aggressive and resistant forms of cancer. The epidermal growth factor receptor (EGFR) is a receptor that medications target for cancer treatment. Objective: The present study employs computational approaches to explore the anticancer activity of newly identified indole alkaloids from Zanthoxylum nitidum against EGFR kinase. Method: Computational techniques, including molecular docking, density functional theory (DFT), and in-silico pharmacokinetic studies, were employed to evaluate the ligand-target interactions. Additionally, drug-likeness was assessed using the Lipinski rule of five. Result and Discussion: We evaluated their pharmacokinetics, binding interactions, and stability using molecular docking, drug-likeness prediction, absorption, distribution, metabolism, and excretion (ADMET) profiling, simulations study, and density functional theory (DFT) study. Nitidumalkaloid C showed remarkable binding affinity (-9.7 kcal/mol) to epidermal growth factor receptor tyrosine kinase, while that of standard drugs showed dacomitinib (-9.0 kcal/mol) and osimertinib (-7.9 kcal/mol). The molecular dynamics MD simulation study revealed stable interactions, with nitidumalkaloid C exhibiting the highest stability. These findings indicate indole alkaloids as potentially effective anticancer medicines, with nitidumalkaloid C demanding further modification for pharmaceutical development. This research informs nitidumalkaloid C as a potential indole alkaloid by providing insights into molecular characteristics and binding energies. Conclusión: These parameters allow consideration of the most promising candidate, nitidumalkaloid C, for novel anticancer drug development to overcome gene mutations or resistance in EGFR-TK.