Computational Identification of Bioactive Molecules from Caralluma stalagmifera L. as Potential VEGFR2 Inhibitors for Endometriosis Treatment

Objectives Endometriosis is a gynecological condition characterized by the growth of uterine tissue outside the uterus, primarily affecting the peritoneal cavity and disrupting the female reproductive system due to estrogen. This study investigates the potential of phytochemicals from Caralluma stalagmifera L. to inhibit Vascular Endothelial Growth Factor Receptor-2 (VEGFR2), which plays a crucial role in blood vessel formation and inflammation associated with endometriosis.

Gas Chromatography-Mass Spectrometry (GC-MS) analysis was utilized to identify active compounds in Caralluma stalagmifera L., particularly those with anti-inflammatory properties. Key compounds included ethyl 2-[(4R,6R)-2,2-dimethyl-6-pentyl-1,3-dioxan-4-yl]acetate and Thioacetic acid S-(tetrahydro-2 H-pyran-3-yl) ester. Molecular docking and Molecular Dynamics (MD) simulations were conducted to examine their interactions with VEGFR2.

Among the compounds tested, ethyl 2-[(4R,6R)-2,2-dimethyl-6-pentyl-1,3-dioxan-4-yl]acetate displayed the most favorable docking score with VEGFR2. The stability of this interaction was further supported by Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) analyses, which demonstrated minimal fluctuations during simulations. Additionally, hydrogen bond formations between the compound and VEGFR2 were observed, suggesting a stable binding environment. The binding free energy calculations reinforced the potential of this compound as a viable inhibitor. Furthermore, Density Functional Theory (DFT) analysis provided insights into the electrostatic properties of the ligand-protein complex, highlighting its stability and interaction dynamics compared to synthetic drugs.

Phytochemicals from Caralluma stalagmifera L., especially ethyl 2-[(4R,6R)-2,2-dimethyl-6-pentyl-1,3-dioxan-4-yl]acetate, show promise in inhibiting VEGFR2, suggesting their potential as therapeutic agents for managing inflammation in endometriosis. Further studies are needed to validate these findings and assess their clinical applications. Similar content being viewed by others Data Availability The data offered in this study are available in this document.

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JJSR thanks Alagappa University: DST- Fund for Improvement of S&T Infrastructure in Universities and Higher Educational Institutions (FIST) (SR/FST/LSI-667/2016)(C); DST-Promotion of University Research and Scientific Excellence (PURSE) (No. SR/PURSE Phase 2/38 (G), 2017 and MHRD-RUSA 2.0, New Delhi (F.24-51/2014-U, Policy (TNMulti-Gen), Dept. of Edn. Govt. of India, Dt.09.10.2018. Tamil Nadu State Council for Higher Education (TANSCHE-RGP) (RGP/2019-20/BU/HECP-0018; Dt.27.04.2021). This research was supported by Researchers Supporting Project number (RSP2025R27), King Saud University, Riyadh, Saudi Arabia. We are thankful for the support provided by UCSI University for the support provided by the Research Excellence and Innovation Grant (REIG) with code REIG-FPS-2022/036. Funding N/A. Author information Authors and Affiliations Contributions S. Balasubramanian: Conceptualization, Investigation, data validation and writing original draft. J. Joseph Sahayarayan: Project administration, Conceptualization, Supervision, writing review and editing. M. Arun: Validation and writing review. K. Soundar Rajan: Writing draft. C. Rajasekar & R. Rajendran: Conceptualization and methodology for phytochemical analysis, Writing review. Saud Alarifi: Writing review. Anis Ahamed: Writing review. Ravishankar Ram Mani: Project administration, Conceptualization, Editing and Writing review. Soon Woong Chang: Writing review. Balasubramani Ravindran: Editing and Writing review. Corresponding authors Ethics declarations Ethical Approval There is no ethical issue in this work. Institutional Review Board N/A. Conflict of Interest N/A. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Jesudass, J.S., Sivaprakasam, B., Kulanthaivel, S.R. et al. Computational Identification of Bioactive Molecules from Caralluma stalagmifera L. as Potential VEGFR2 Inhibitors for Endometriosis Treatment. J Pharm Innov 20, 18 (2025). https://doi.org/10.1007/s12247-024-09894-y Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s12247-024-09894-y