• Investigating Isoquercetin vs. Fluoxetine effects on SERT by molecular docking method
  • Hossein Azimi Bashar,1,*
    1. Islamic Azad University Pharmaceutical Sciences Branch


  • Introduction: The protein known as SERT is crucial for the uptake of serotonin from the synaptic cleft back into the presynaptic neuron. Dysfunction in SERT activity can result in depression and anxiety; therefore, this protein is a key target in treating neuropsychiatric disorders such as major depressive disorder (MDD). Selective serotonin reuptake inhibitors (SSRIs) are a common type of antidepressive agent. They increase serotonin activity by inhibiting SERT. Fluoxetine is one of the most commonly used SSRIs. Isoquercitrin, alongside rutin, is considered one of the major glycosidic forms of the natural flavonol quercetin. Medicinal herbs, fruits, vegetables, and plant-based foods and beverages frequently isoquercitrin. Across both in vitro and in vivo studies, Isoquercitrin demonstrates a broad spectrum of positive biological effects, with a particular focus on its chemoprotective ability against oxidative stress, cancer, and cardiovascular disorders. This research project compares the binding affinity between Isoquercetin and Fluoxetine with the serotonin reuptake transporter using the molecular docking method. Exploring the possibility of Isoquercetin forming a stronger attachment with SERT than Fluoxetine could lead to the discovery of novel medicinal compounds derived from Isoquercetin.
  • Methods: In this research, the structure of SERT was first downloaded from the Uniprot website. Preparations, such as the addition of charge and hydrogen ions, were then executed using Chimera software. The three-dimensional structures of Isoquercetin and Fluoxetine were obtained from the PubChem website. The SERT protein binding site was determined using Deepsite. [Center; X: 36.4195, Y: 184.783, Z: 142.7143 and Dimensions (Angstrom); X, Y, Z: 25.00] Finally, the molecular docking process was carried out using AutoDock Vina in PyRx 0.8 to investigate the binding affinity of Isoquercetin and Fluoxetine to SERT.
  • Results: The docking process carried out with PyRx software led to these results. The data is associated with each model's binding affinity, lower RMSD bond, and upper RMSD bond. Isoquercetin: Model #1: [ -9.4, 0.0, 0.0] Model #2: [ -9.3, 2.255, 3.655] Model #3: [ -9.1, 2.069, 3.563] Model #4: [ -9.1, 1.618, 2.285] Model #5: [ -9.0, 2.422, 7.057] Fluoxetine: Model #1: [ -8.9, 0.0, 0.0] Model #2: [ -8.8, 0.168, 1.681] Model #3: [ -8.2, 1.941, 2.609] Model #4: [ -8.1, 5.403, 7.374] Model #5: [ -7.9, 4.582, 5.997]
  • Conclusion: According to the results of the molecular docking analysis of Isoquercetin and Fluoxetine with SERT, both compounds revealed negative binding energy. However, Isoquercetin revealed a higher affinity compared to Fluoxetine. This indicates that new therapeutic drugs can be developed using Isoquercetin to treat major depressive disorder.
  • Keywords: Isoquercetin, Fluoxetine, SERT, Molecular docking, Major depressive disorder