IN-SILICO SCREENING OF PHYTOCHEMICAL COMPOUNDS IN CAESALPINIA BONDUCELLA L. SEEDS AGAINST THE GENE TARGETS OF OVARIAN STEROIDOGENESIS PATHWAY

Abstract

Polycystic ovary syndrome (PCOS) is the most common gynaecological disorder among reproductive-age women. Impaired metabolism of androgens and estrogens is one of the leading causes of PCOS. In India, medicinal herbs are being explored for their anti-androgenic and anti-estrogenic properties. In this study, we have screened the seed extracts of the herbal plant, Caesalpinia bonducella for potent inhibitors of estrogen and testosterone biosynthesis and assimilation. Methanol extract of C. bonducella seed kernels were subjected to gas chromatography - mass spectrometry (GC-MS) to identify the phytochemical constituents. Out of forty-three phytochemical compounds identified from the extract, eight compounds were selected based on Lipinski's rule of five for molecular docking. The selected phytochemical compounds were docked against specific targets of ovarian steroidogenesis pathway; human aromatase (CYP19A1), human 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1), human androgen receptor and estrogen receptor α. Further, the nature of these compounds was validated using density functional theory (DFT) calculations and ADME/T studies. As per the molecular docking output, compounds 33, 35, 38, 40, and 43 exhibited higher binding affinities against the four selected targets. Phytochemical compounds were optimized using Gaussian 16 with the B3LYP function and the 6-31G(d, p) basis set and were correlated with docking results. ADME/T helps in identifying the potential drug candidates from a pool of drugs. Five phytochemical compounds, 33, 35, 38, 40, and 43 were found to have the ability to bind and inhibit appropriate targets in the ovarian steroidogenesis pathway. Hence, these compounds can be further characterized in vitro and in vivo for alleviating PCOS.