Targeting NUDT5 For Breast Cancer Therapy: In-Silico Identification of Potent Inhibitors From Terminalia chebula

Breast cancer is a leading cause of mortality, particularly in low- and middle-income countries, necessitating the discovery of novel therapeutic agents. NUDT5, an enzyme critical in hormone-dependent gene regulation, presents a promising target for breast cancer treatment. This study aimed to identify potential NUDT5 inhibitors from 38 compounds derived from the Myrobalan plant (Terminalia chebula) using molecular docking techniques. Ellagic Acid emerged as the most potent inhibitor with a binding affinity of -9.1 kJ/mol. ADME analysis of Ellagic Acid revealed favorable pharmacokinetic properties, including high gastrointestinal absorption and no blood-brain barrier permeability, with a predicted volume of distribution of 0.32 L/kg and a total clearance rate of 15.4 mL/min/kg. Toxicological assessments confirmed that the compound is non-carcinogenic, non-hepatotoxic, and free from significant adverse effects. Molecular interaction studies highlighted that Ellagic Acid forms stable complexes with NUDT5, establishing fifteen Pi-Pi stacked interactions and three conventional hydrogen bonds. These comprehensive analyses suggest that Ellagic Acid from Terminalia chebula is a promising candidate for breast cancer therapy, suggesting further experimental validation through in vitro and in vivo studies.