This study explores the potential leads from Pongamia pinnata ( P. pinnata ) flower phytochemicals against prostate cancer through network pharmacology, molecular docking, MMGBSA analysis and molecular dynamics (MD) simulations. Out of 25 compounds screened, Pongaglabrone, 3'-Methoxypongapin, Pongapin, Ovalitenone, and Ovalichromene demonstrated stronger binding affinities toward Human Anti-Prostate-Specific Antigen (PSA) than Sorafenib, a reference anticancer drug. Docking results revealed that these compounds interact with key PSA active site residues, suggesting their role as natural PSA inhibitors. Network pharmacology analysis identified multi-target interactions with cancer-related proteins such as HSP90AA1, STAT1, and HIF1A, indicating a broad mechanism of action. ADME profiling supported the drug-likeness of Pongaglabrone and Pongapin based on favorable absorption and excretion properties along with toxicity prediction some mild organ toxicity risks were predicted. To validate docking results, 100-nanosecond MD simulations were performed for Pongaglabrone and 3'-Methoxypongapin in complex with PSA. Both ligands demonstrated structural stability with RMSD values between 1.8–2.7 Å, stable radius of gyration, and consistent hydrogen bonding. These findings confirmed the stable binding and conformational integrity of the complexes. The integrated computational approach highlights P. pinnata phytochemicals particularly Pongaglabrone and 3'-Methoxypongapin as potential leads for prostate cancer therapy, warranting further experimental validation.
Saravanan et al. (Wed,) studied this question.