Identification a Novel Inhibitor for Aldo�Keto Reductase 1 C3 by Virtual Screening of PubChem Database

Abstract

Aldo�keto reductase1C3 (AKR1C3) is an enzyme with important roles in the metabolism of steroids. AKR1C3 inhibition is a target in cancer treatment. In this study, compounds similar to Stylopine, a strong inhibitor of AKR1C3, were investigated by virtual screening. At the first stage, compounds similar to the Stylopine were excluded from the PubChem database. Then, molecular optimization in Hyperchem software and virtual screening in PyRx software was conducted. Finally, selected compounds were examined by AutoDock to find the compound with the best inhibitory effect. Among 20 selected similar structures to Stylopine in PubChem, 12 molecules had the highest binding affinity by analyzing in PyRx. Subsequently, 5 compounds (8, 21, 32, 35, and 39) were analyzed for ligand and enzyme docking. The ligand number 32 had the best binding affinity and inhibition constant (ki) in comparison with Stylopine. This compound had lower ki than the Stylopine in this research. So, it might inhibit AKR1C3 better than Stylopine. The compound can be studied as a strong inhibitor of AKR1C3 in future in vitro and in vivo researches. © 2022, The National Academy of Sciences, India