Abstract This study was aimed at finding the phytochemicals that could specifically target harmful mutations in CDKN2A linked to cervical cancer was performed. The E61D mutation in the CDKN2A gene was identified and confirmed to be deleterious using multiple computational prediction tools. To explore potential therapeutic candidates, the molecular structures of 650 phytochemical compounds were retrieved from PubChem, followed by comprehensive ADME (Absorption, Distribution, Metabolism, and Excretion) analysis to assess their drug‐likeness and pharmacokinetic properties, hepatotoxicity, cytotoxicity, carcinogenicity, immunogenicity, and mutagenicity of ligands were determined by a web server known as ProTox‐II. Among 650 different phytochemicals only 14 compounds were retained after ADME and toxicity analysis. Three compounds named as Neoechinulin, 2,4‐difluoro‐N‐4‐(2‐sulfanylacetyl)phenylbenzene sulfonamide, and Belinostat showed highest binding affinities and among them Neoechinulin having the highest binding affinity (–7.4 kcal/mol) with mutated CDKN2A protein was selected for simulation studies. Molecular dynamics simulations over 100 ns further confirmed the stability of the Neoechinulin–CDKN2A complex, with consistent RMSD, minimal fluctuation in binding residues, and stable compactness (Rg), indicating strong and sustained binding. These computational findings collectively position Neoechinulin as a promising lead candidate with high binding affinity, structural stability, and favorable pharmacokinetic properties. By targeting the underexplored E61D mutation, this study introduces a novel in silico research that not only identifies phytochemical inhibitors however, it also demonstrates their mechanistic potential through dynamic structural analysis. The findings support these compounds as promising, low‐toxicity, multi‐target therapeutic candidates, laying the groundwork for cost‐effective precision drug development. However, further experimental validation is necessary to confirm their clinical relevance in personalized treatment strategies for CDKN2A‐mutated cervical cancer.
Naveed et al. (Thu,) studied this question.