Exploring phytochemical as potential inhibitors of human DNA polymerase β for targeted ovarian cancer therapy: An In-Silico approach.

Ovarian cancer poses significant challenges due to limited treatment options and high mortality rates, necessitating innovative therapeutic strategies. Targeting DNA repair pathways, such as DNA polymerase β (Pol β), holds promise for improving treatment outcomes. This study aims to identify phytochemicals from the SuperNatural database as natural inhibitors of Pol β activity to enhance ovarian cancer therapy efficacy, particularly when used in combination with damaging agents. Screening 21,105 drug-like molecules and 800 NatProd molecules based on Lipinski's rule of five, Golden Triangle rule, and Pfizer’s rule, followed by the removal of compounds with predicted carcinogenicity, toxicity, and mutagenicity, resulted in 1,104 molecules for structure-based virtual screening. Docking-based virtual screening using two servers was conducted on selected molecules, followed by computer simulations to assess their interaction dynamics and stability with Pol β. Molecular dynamics simulations further evaluated stability and interactions, considering energy, forces, and interaction scores. From these analyses, four promising Pol β inhibitors—SN00158342, SN00305418, SN00004251, and SN00341636—were identified, exhibiting favorable stability profiles and interactions. Utilizing these compounds alongside DNA-damaging agents presents a novel and potentially fruitful approach to improving ovarian cancer treatment outcomes. Overall, this study underscores the potential of phytochemicals as effective Pol β inhibitors, offering a promising avenue for enhancing ovarian cancer therapy effectiveness.