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FLAVONOID PHYTOPROGESTIN COMPOUNDS AS PROGESTERONE RECEPTOR MODULATORS FOR ENDOMETRIUM RECEPTIVITY: A SYSTEMATIC SCREENING AND AN IN SILICO ANALYSIS

IKA WIDIAWATI 1, HERI SETIAWAN 1,2*, ANDISYAH PUTRI SEKAR1, BERNA ELYA 3,NAJIHAH BINTI MOHD HASHIM 6, REZI RIADHI SYAHDI 4,5

1Department of Pharmacology, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
2National Metabolomics Collaborative Research Center, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia 3Department of Pharmacognosy, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
4Computational Biology and Bioinformatics Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia 5NARA Institute of Science and Technology, Japan
6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

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Herbal medicines are gaining popularity as an alternative treatment for women's health problems, especially infertility. Phytoprogestins are compounds derived from natural ingredients with progestogenic activity and can be used as an alternative treatment to eliminate undesirable side effects due to hormonal therapy. This study aimed to screen phytoprogestin compounds that exhibit a binding affinity for the progesterone receptor (PR) using virtual screening and molecular docking. A PRISMAguided systematic search of flavonoid compounds from PubMed and ScienceDirect literature databases resulted in nine selected flavonoid compounds: baicalein, daidzein, decursinol, liquiritigenin, irilone, naringenin, glycyrrhizin, kaempferol and apigenin. These compounds were subjected to molecular docking simulation for the progesterone receptor (PR, PDB ID: 1A28) using Chimera, the PyRx docking tool and Biovia Discovery Studio 2021 for visualisation. The results showed that only 4 of the screened ligands are potential drug candidates compared to native ligand progesterone (-11.3 kcal/mol) based on the docking scores and all the other necessary analyses, such as drug-likeness and ADMET profiling. These compounds are apigenin (-9.2 kcal/mol), kaempferol (-9.1 kcal/mol), baicalein (-8.9 kcal/mol) and naringenin (-9.2 kcal/mol). Apigenin and kaempferol showed the most potential activity for PR compared to naringenin, according to their several hydrogen bonds and hydrophobic interactions. Meanwhile, baicalein is the weakest compound because it only showed three hydrophobic interactions.