Computational Evidence for the Anticancer Activity of Phytochemical Constituents of Terminalia Chebula: An In‐Silico Attempt

Abstract

AbstractNatural compounds represent Secondary metabolites shaped and endorsed by nature over countless years, showcasing both unique chemical variety and a corresponding range of bioactivities, along with drug‐like attributes. Plant‐derived remedies are projected to comprise approximately 25 % of pharmaceuticals in developed nations. Terminalia chebula earns its title as the “King of medicines” due to its multifaceted pharmacological properties. The phytochemical elements within Terminalia chebula were assessed for their interaction with the human dihydrofolate reductase enzyme (5HT4.pdb) due to its significant role in the development of colorectal cancer. The American Cancer Society provides updated CRC statistics based on incidence from population‐based cancer registries and mortality from the National Center for Health Statistics. In 2023, approximately 153,020 individuals will be diagnosed with CRC and 52,550 will die from the disease, including 19,550 cases and 3750 deaths in individuals younger than 50 years. The compounds TC2 (−8.61 Kcal/mol), TC15 (−7.02 Kcal/mol), and TC23 (−6.98 Kcal/mol) demonstrated higher glide scores. Additionally, TC2 (−71.21 Kcal/mol), TC12 (−101.63 Kcal/mol), TC15 (−81.40 Kcal/mol), and TC29 (−77.47 Kcal/mol) exhibited stronger binding affinities (ΔG Bind) to the target. Based on the outcomes of both docking and MM‐GBSA analyses, TC2 was selected for further investigation via molecular dynamics (MD) simulations, which illustrated the stability of the TC2/5HT4 complex. Among the top‐ranked compounds, TC2 adhered to Lipinski's guidelines for drug‐likeness without any violations. Inhibiting the human DHFR enzyme indirectly hampers the progression of colon cancer. The findings from this in‐silico investigation serve as a foundational basis for potential in vitro and in vivo research.