Identification of Probable Plant-based Oral Contraceptives from Cissampelos Pareira using Virtual Screening and Molecular Dynamics Simulation Studies

One of the major concerns of today is the population explosion. India, being the second most populated country, contributes over 17.7% to the world population. One of the most effective ways of population control is the use of oral contraceptives. Most of the oral contraceptives are either natural or synthetic hormonal derivatives. Although they are proven for their efficacy and reliability, they exhibit many adverse effects ranging from mild effects like headache and mood swings to severe effects like increased risk of ovarian, cervical and endometrial cancers and menstrual cycle disruption. Therefore, there is a need for identifying oral contraceptives with minimal or no adverse effects. In some places of India, especially in the north-east, the plant Cissampelos pareira is being used as a folklore medicine for female contraception. Previous study has shown that the methanolic leaf extract of the plant had significant female contraceptive activity in vivo. In the present study, we used in silico methods to screen reported compounds of the plant for their agonistic activity with human estrogen receptor α (ERα). We have used Maestro (Schrӧdinger) for virtual screening. PDB protein 1G50 (crystal structure of ERα bound to estradiol) was taken and protein preparation using protein preparation wizard tool was carried out. A library of all the reported compounds from the plant was created by extensive literature search and ligand preparation was done using Ligprep tool. Docking was performed and the compounds exhibiting good docking score, binding energy and induced fit docking scores were identified. The hits were taken forward for molecular dynamics (MD) simulation studies using Desmond with OPLS3 force field model. The top hit was found to be coclaurine (C17H19NO3) with a docking score of -10.324. The protein-ligand interactions were comparable to the standard estradiol with ERα and the MD simulation studies indicated that the ligand might form a stable complex with the receptor indicating its probable agonistic activity.