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

Abstract

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.

Methods

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.

Results

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.

Conclusions

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.