Pharmacoinformatics based in silico Molecular Dynamics Simulation for Screening Phytochemicals as AMPK and INSR Modulators for Polycystic Ovarian Syndrome from Medicinal Plants

Author: Sudhakar Pachiappan, Arul Balasubramanian, Murali G. and Kothai Ramalingam

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Abstract

Polycystic ovarian syndrome (PCOS) is a complex endocrinal and metabolic disorder of women of reproductive age women. PCOS is characterized by hyperandrogenism, irregular periods, cyctic ovaries, insulin resistance, hyperinsulinemia, obesity, and dyslipidemia resulting in an increased risk of diabetes and cardiovascular diseases. Due to its complexity and lack of systemic treatment, we have selected three plant materials S. asoca bark, G. sylvestre leaves, and P. daemia aerial parts, which are prominent and effective against any two or more major pathogenic pathways of PCOS to identify effective alternative drug molecules. The Phytoconstituents of the selected plant materials were retrieved from IMPPAT, Dr. Duke’s public database, and also manually searched from articles. PubChem database was used to obtain the structures of the selected phytochemicals. Graph theoretical analysis was employed by exploitation of the KEGG pathway and finding out the significant PCOS pathways and the influential proteins such as AMPK and INSR. The retrieved compounds were docked against a selected target using Schrodinger Glide software, and ADMET studies were carried out in a web-based online tool. Compounds that possess superior molecular interaction and kinetic profiles were further selected for molecular dynamics studies. The identified 65 compounds were docked with the selected targets. A compound that has high docking score from each plant against each target was selected for further ADMET and molecular dynamic (MD) studies. These compounds with each target having docking scores in the range of (-11.09 to -1.14 kcal/mol) with AMPK and (-12.92 to -1.43 kcal/mol) with INSR. The selected compounds were further screened for ADMET studies through an online Swiss ADME and pkCSM web server. Based on the ADMET and docking results two compounds from each target that have higher docking scores, pharmacokinetic, and safety profiles were selected for MD studies. The MD results showed that β-sitosterol showed better intermolecular interaction and stability against AMPK and Gymnemoside E against INSR. These aforementioned findings interpreted that the β-sitosterol and Gymnemoside E have adequate potential as drug candidates for the treatment of PCOS. Further in vivo studies are needed to explore these constituents for clinical use.

Keywords

ADMET, AMPK, INSR, Docking, Molecular Dynamics, Polycystic Ovarian Syndrome

Conclusion

Based on these in silico studies the phytoconstituents β-sitosterol and Gymnemoside E were identified as significant drug candidates for polycystic ovarian syndrome through activating AMPK and INSR target protein medicated pathway improves follicular development and ovulation by altering hyperandrogenism and insulin resistance in PCOS ovary. Further scope full in-vitro and in-vivo studies are required to explore these phytoconstituents as better drug candidates for PCOS.

References

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How to cite this article

Sudhakar Pachiappan, Arul Balasubramanian, Murali G. and Kothai Ramalingam (2023). Pharmacoinformatics based in silico Molecular Dynamics Simulation for Screening Phytochemicals as AMPK and INSR Modulators for Polycystic Ovarian Syndrome from Medicinal Plants. Biological Forum – An International Journal, 15(5): 1087-1092.