In Silico Analysis of Plant-Based Bioactive Compounds Targeting Progesterone Receptors for the Treatment of Uterine Leiomyoma

Abstract

Uterine leiomyomas are the most common benign gynaecological tumours that affect 50% - 60% of females belonging to reproductive age. The role of progesterone in the growth and development of leiomyomas is evident. Progesterone is regulated by progesterone receptors and it acts by activating PI3K/AKT pathway, by increasing proliferating cell nuclear antigen (PCNA) levels and Bcl-2 expression. Thus, modulating the receptor can help in the treatment of leiomyomas. The current study involves testing the efficiency of the various plant-based bioactive compounds to bind to the progesterone receptors, which may possess inhibitory or modulatory effects on or against progesterone receptors. These compounds can be further experimented with using other in vivo and in vitro methods to produce phytomedicine based on drugs for the treatment of uterine leiomyomas. This study is an in silico analysis performed using various bioinformatics databases and software. The receptor and ligand structures were retrieved from PDB and PubChem databases. Their pharmacokinetics and pharmacodynamics properties were analyzed using various databases. AutoDock4.2.6 was used for molecular docking, and the results were visualized using LigPlot+. Among 15 compounds selected, 8 compounds had higher binding energies than the control drug Ulipristal acetate i.e., -8.21Kcal/mol. Of which Ursolic acid, Vitamin-D2, and Betulinic acid had binding energies above -9.0 Kcal/mol. This concludes that these compounds can modulate the progesterone receptors, thus decreasing the proliferation and growth of uterine leiomyomas. Further studies can bring out the potential therapeutic effects of these bioactive compounds and they can act as a potential lead compound in the design of novel drug targets for the treatment of uterine leiomyoma.