In Silico Study of the 5-Hydroxytryptamine-2C Receptor Antagonist Activity of Anthocyanins as Antidepressant Therapy

This study aimed to evaluate the drug-likeness, pharmacokinetic and safety prediction of six types of anthocyanins (ANC) as well as virtual molecular interaction between ANC and 5-hydroxytryptamine-2C (5HT-2C) receptor for antagonist target of antidepressant drug development. The Lipinski rule of five was used to predict the oral drug-likeness of ANC. The pharmacokinetic and safety prediction was analyzed with a free accessible web server. The ligands of ANC were retrieved from PubChem National Centre for Biotechnology Information (NCBI) database. The protein of the 5HT-2C receptor was obtained from Protein Data Bank. Molecular docking was performed by PyRx software and visualized using Discovery Studio Software. The results showed ANC is proposed as an oral drug candidate. The pharmacokinetic prediction of ANC was demonstrated to have high absorption in the intestinal route, solubility in the aqueous phase, capability to evade hepatic first-pass metabolism and high total clearance from the kidney. Virtual toxicity prediction showed a higher threshold of chronic lethal dose than control with no toxicity on the salmonella typhimurium reverses mutation assay (AMES) test, liver, and skin. Molecular prediction found ANC type of delphinidin has the most similar interaction site with the control antagonist ligand on the 5HT-2C receptor which is facilitated with hydrogen bonds and hydrophobic bonds at amino residues of Trp324, Phe328, Ala222 and Val135. We concluded ANC particularly delphinidin is proposed as an oral drug candidate potentially used as a 5HT-2C receptor antagonist and thus, further in vitro and in vivo studies are necessary to confirm the effect on antidepressant activity.