Targeting Cancer Hallmarks Through Phytochemicals: An in-Silico Docking Study of Natural Compounds as Inhibitors of Key Oncoproteins

Cancer is a primary cause of morbidity and mortality worldwide and represents a substantial burden on health care systems. In 2020, there were more than 19.3 million new cases and over 10 million deaths from cancer annually. Despite the progress in traditional therapy, problems like as drug resistance, toxicity and recurrence are still present. Medicinal plant phytochemicals have attracted a lot of interest in the recent years as potential anticancer medications because of their structural diversity, biological activity and relatively low toxicity. The study was conducted to evaluate the anticancer efficacy of some phytochemicals extracted from five traditionally used medicinal plants i.e. Curcuma longa (turmeric), Azadirachta indica (neem), Allium sativum (garlic), Solanum lycopersicum (tomato) and Withania somnifera (ashwagandha) against important oncogenic protein targets by using a structure based molecular docking methodology. A preliminary screening of more than 60 phytochemicals was identified by a detailed literature study and validated by the IMPPAT 2.0 database. The proteins KRAS, EGFR, HER2, HRAS and CTNNB1 crystal structures were retrieved from the RCSB Protein Data Bank. The three-dimensional ligand structures were retrieved from the PubChem database. Molecular docking simulation was performed using CB-Dock2 platform. CB-Dock2 predicts the ligand-protein binding affinity by integrating cavity detection and scoring mechanism of AutoDock Vina. The maximum binding affinity was observed with azadiradione from Azadirachta indica with KRAS (Vina score = –15.3 kcal/mol) showing a somewhat persistent association in the active region of the protein. Other important chemicals included bisdemethoxycurcumin binding to HRAS (–9.4 kcal/mol), sitoindosidelx interacting with EGFR (–10.7 kcal/mol) and nicotiflorin targeting KRAS (–10.9 kcal/mol). Beta-carotene, isotretinoin, and zeaxanthin, carotenoid chemicals from Solanum lycopersicum, showed strong interactions with HER2. The results suggest that phytochemicals from medicinal plants like turmeric, ashwagandha and neem have great anticancer potential and might be lead molecules for developing novel medications.

Phytochemicals, Molecular Docking, Anticancer Activity, Oncogenic Proteins

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