Computational evaluation of pongamol interactions with potential molecular targets of Blastocystis hominis

Abstract Pongamol, a bioactive substance that occurs naturally, shows promise as a treatment that targets several molecular pathways associated with Blastocystis hominis infection. Its binding affinity, pharmacokinetic behaviour, and protein-chemical interactions were examined in this work using molecular docking, ADMET profiling, and STITCH network analysis. Docking analysis predicted favorable binding of pongamol to eight selected protein targets, with the lowest docking scores observed for squalene epoxidase (− 9.7 kcal/mol), dihydrofolate reductase (− 8.9 kcal/mol), adenosine deaminase (− 8.6 kcal/mol), and thioredoxin reductase 1 (− 8.2 kcal/mol). These findings indicate that pongamol may interact with proteins involved in processes related to sterol metabolism, nucleotide metabolism, and redox regulation. However, the docking results represent predicted binding interactions and do not establish enzymatic inhibition or biological efficacy. The ADMET analysis predicted high gastrointestinal absorption, blood–brain barrier permeability, and favorable drug-likeness, but also indicated inhibition of CYP1A2, CYP2C19, CYP2C9, and CYP3A4, as well as potential hepatotoxicity and reproductive toxicity concerns. These in silico results support further investigation of pongamol as a computationally prioritized multi-target candidate against Blastocystis hominis . However, experimental studies are required to determine whether pongamol truly inhibits these targets or exhibits antiparasitic activity.