In Silico Evaluation of Natural Phenolic Compounds Targeting the S1P1 Receptor and Cardiovascular-Related Protein Targets: Molecular Docking and ADMET Analysis

Abstract

The aim of this study was to evaluate the potential interactions of selected phenolic compounds with the S1P1 receptor and cardiovascular-related protein targets using molecular docking, and to investigate their pharmacokinetic and toxicological properties via in silico ADMET analysis. Six different protein structures (PDB: 3VY2, 7C4S, 7TD3, 7VIE, 7VIF and 7WF7) were obtained from the Protein Data Bank database. Apigenin, fisetin, kaempferol, quercetin, resveratrol and rosmarinic acid were used as ligands. Molecular docking analyses were performed using AutoDock Vina software, and the most suitable binding positions were determined based on RMSD and binding energies. Furthermore, ADMET properties were evaluated using ADMETlab 3.0. All compounds exhibited suitable binding affinity for the selected protein targets. Docking scores ranged from -7.2 to -9.3 kcal/mol. Apigenin and rosmarinic acid demonstrated stronger and more consistent binding profiles compared to the other compounds. Interaction analyses have shown that hydrogen bonds, π–π interactions and hydrophobic contacts play a significant role in complex stability. According to ADMET analysis, apigenin exhibited better membrane permeability, whilst rosmarinic acid presented a more stable metabolic profile. The findings suggest that apigenin and rosmarinic acid, in particular, may be potential therapeutic candidates for the S1P1 receptor and cardiovascular-associated proteins. However, further in vitro and in vivo studies are required to validate these results.

Keywords

• Molecular docking
• Natural polyphenols
• Cardiovascular diseases
• Endothelial function
• Cellular perfusion
• Vascular biology

Ethical Statement

Ethics committee approval was not obtained as no studies on animals or humans were conducted in this study.

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