Therapeutic capability of selected medicinal plants' bioactive constituents against the mutant ovarian TP53 gene; a computational approach

Abstract

A mutant P53 protein plays such a crucial role in ovarian cancer, and natural compounds have been known to be effective in treating cancer. The current study was conducted to discover new mutant P53 modulators in plants used for medicinal purposes. The mutant p53 3D structure was built using homology modeling, while its active binding domain was predicted using Findsitecom2.0. Docking studies were conducted with ligands derived from bioactive components of seven different plants and mutant p53 binding sites. Autodocking programs, including Discovery Studio and PyRx, were used to obtain the docking protein and its intricate visual representation. Gemcitabine and thiotepa were the reference drugs. Acute RAT toxicity and Pharmacokinetic properties were utilized in Gusar and SWISSADME, respectively, to narrow down the hit compounds to those with the highest binding affinities. Using the density functional theory (DFT) method, the electronic properties of the bioactive constituents were determined. 15 of the 50 bioactive phytochemicals displayed superior mutant p53 binding energies compared to Gemcitabine and Thioteba (−5.4 and −3.5 binding scores, respectively). Considering acute toxicity predictions and pharmacokinetics, 10-hydroxycamptothecin, irinotecan, morusin, and rubitecan were the four major compounds with low toxicity. DFT calculations uncovered regions susceptible to nucleophilic and electrophilic assaults. The study sought to identify potential drug candidates for modulating mutant P53 in ovarian cancer treatment.