Computational investigation of four isoquinoline alkaloids against polycystic ovarian syndrome

Hyperandrogenism, insulin resistance, and estrogen dominance are the prime defining traits of women with polycystic ovarian syndrome which disrupts hormonal, adrenal, or ovarian functions resulting in impaired folliculogenesis and excess androgen production. The purpose of this study is to identify an appropriate bioactive antagonistic ligand from isoquinoline alkaloids [palmatine (PAL), jatrorrhizine (JAT), magnoflorine (MAG) and berberine (BBR)] from stems of Tinospora cordifolia. Phytocomponents inhibit/prevent androgenic, estrogenic, and steroidogenic receptors, insulin binding, and resultant hyperandrogenism. Intending to develop new inhibitors for human androgen receptor (1E3G), insulin receptor (3EKK), estrogen receptor beta (1U3S), and human steroidogenic cytochromeP450 17A1 (6WR0), here we report the docking studies by employing a flexible ligand docking approach using AutodockVina 4.2.6. ADMET screened swissADME and toxicological predictions to identify novel and potent inhibitors against PCOS. Binding affinity was obtained using Schrodinger. Two ligands, mainly BER (−8.23) and PAL (−6.71) showed the best docking score against androgen receptors. A molecular docking study reveals that compounds BBR and PAL were found to be tight binder at the active site of IE3G. Molecular dynamics results suggest that BBR and PAL showed good binding stability of active site residues. The present study corroborates the molecular dynamics of the compound BBR and PAL, potent Inhibitors of IE3G, having therapeutic potential for PCOS. We project that this study's findings will be helpful in drug development efforts targeting PCOS. Hence isoquinoline alkaloids (BER& PAL) have potential roles against androgen receptors, and in specific PCOS, scientific evaluation has been put forth based on virtual screening.Communicated by Ramaswamy H. Sarma