Uncovering the Natural Inhibitors From Medicinal Plants to Alleviate Human Cancers Targeting the p53 Protein: An In Silico Approach

Abstract The tumor suppressor p53 protein plays a key role in controlling several essential cellular responses, including cell growth, development, and apoptosis, helping to prevent cancer development. In various cancers, loss of p53 function results in prolonged cell replication and inhibition of programmed cell death. There are a few options available to target p53, but they come with limitations. For this reason, there is a need for novel drug candidates to maintain p53 functionality. Therefore, our study aims to identify potential natural bioactive compounds through comprehensive in silico methods such as molecular docking, MM/GBSA (molecular mechanics generalized born surface area), ADME/T (absorption, distribution, metabolism, excretion, and toxicity), and molecular dynamics (MD) simulation against the targeted protein p53. Initially, 462 phytochemicals from 23 medicinal plants were screened using molecular docking and MM‐GBSA studies to find potential phytochemicals. From the studies, the top three compounds, CID‐3469, CID‐5280372, and CID‐591524, were selected based on their good binding affinities for further investigation, where all the compounds showed better drug‐likeness with no toxicity in ADME/T analysis. MD simulation depicted better structural stability of phytocompounds in complexes with p53 protein. This study shows novel insights into the development of novel bioactive compounds as drug candidates for cancer treatment.