Quercetin and Kaempferol as Potential Modulators of Dopaminergic, Serotonergic, and Estrogenic Receptors: Computational Insights into Female Reproductive Health

Abstract Background Natural polyphenols like kaempferol and quercetin draws interest because of their ability to interact with multiple receptors. This study determines the pharmacokinetic characteristics, stability, and binding dynamics of quercetin and kaempferol. Methods Protein and ligand structures were obtained from the Protein Data Bank and PubChem, respectively. LigPrep and Protein Preparation Wizard (Schrödinger Suite 2023) were used to prepare the ligands and protein, respectively. Docked complexes were prepared subjected to 100 ns MD simulations using Desmond. Both ligands formed stable complexes. Results With variations within 1–3 Å range, the RMSD values for quercetin and kaempferol stabilized at about 50ns, and some earlier. RMSF plots demonstrated consistent interactions with important residues and decreased mobility in ligand-binding areas. Throughout the simulation, PHE, LEU and TRP formed persistent hydrophobic interactions, HIS, SER, THR and ASN formed polar interactions stable hydrogen bonds while GLU and ASP contributes negatively charged interactions. Both kaempferol and quercetin shows excellent metabolic stability and drug-likeness. Kaempferol, shows better ADMET properties and interaction consistency. Conclusions Due to the presence of stable and prolonged activation of ESR2, HTR2C and SLC6A3 the therapeutic value of kaempferol and quercetin in enhancing the sexual health of women is confirmed, with kaempferol showing better profile.