Structure and ligand based high throughput virtual screening against 3-beta hydroxysteroid dehydrogenase type-1 for...

A hormonal disorder that severely affects women's routine physical and emotional life is PCOS (Polycystic Ovary Syndrome). It has been witnessed as a heavily detrimental and most threatening disorder, causing multiple complications, such as type 2 diabetes, cardiovascular disease, and endometrial carcinoma. One of the major causes of PCOS is hyperandrogenism, which results in the dysfunction of the ovaries. The enzyme responsible for such excessive production of androgen is 3-beta hydroxysteroid dehydrogenase-1 (3βHSD1), which is an oxidoreductase that performs multiple functions in steroid metabolism. Trilostane and troglitazone are proposed inhibitors for 3βHSD1 with anticipated side effects. With the aim to identify non-steroidal phytocompounds, structure-based ligand screening against ChEBI was done, which resulted in 3459 compounds. Initially, NAD was docked into the protein to have an active enzyme structure. Then other ligands were docked. Based on a docking score of - 8.0 kcal/mol, ADME properties, and interaction profiling, seven compounds-Aphidicolin, Sagequinone methide A, Premarrubiin, Hoda acetal, Ophiopogonanone A, Brosimacutin C, and Cremastranone-were listed out. All these seven compounds were reported with medicinal importance in the literature. Hence, the stability of protein-ligand complexes was analyzed in detail through 200 ns MD simulation. Results from this study establish these compounds as leads for drug development to combat PCOS.