Computational Screening ofZanthoxylum armatumDC Phytochemicals for inhibiting Mutant P53 in Throat Cancer Therapy

Aim To investigate the potential of phytochemicals from Zanthoxylum armatum DC in targeting mutant p53 as a therapeutic strategy for throat cancer using an in-silico approach. Background Throat cancer is increasingly associated with mutations in the TP53 gene, leading to dysfunctional p53 proteins. Current synthetic drugs targeting mutant p53 face challenges of toxicity and off-target effects, necessitating the exploration of alternative natural compounds. Methods We employed molecular docking, molecular dynamics simulations, MMPBSA analysis, and ADMET studies to identify and characterize effective inhibitors of mutant p53 from Z. armatum DC phytochemicals. Results Three compounds – Z3, Z7, and Z33 – demonstrated superior binding affinities to mutant p53 compared to the commercial drug Prima. These phytochemicals induced more compact and stable protein conformations, with Z3 and Z7 notably restricting active site residual motion. MMPBSA analysis confirmed favourable binding energetics, while ADMET studies indicated drug-like properties with potentially lower toxicity than Prima. Conclusion This study provides compelling evidence for the potential of Z. armatum DC phytochemicals, particularly Z3 and Z7, as novel therapeutic agents targeting mutant p53 in throat cancer. These findings offer a foundation for future experimental validation and drug development efforts.