Protective Effect of Quercetin and p-Coumaric Acid (p-CA) Against Cardiotoxicity: An In Silico Study

Hydroxychloroquine (HCQ) is a common antimalarial drug that has been used effectively in the treatment of various rheumatic and auto-immunity diseases. The major side effects and drawbacks associated with HCQ are cardiotoxicity, retinopathy, gastrointestinal upset, and neuromyopathy however, cardiotoxicity is an increasing concern and it is critical to avoid heart dysfunction induced by HCQ. The present work is focused on receptor and signaling molecules associated with pathways attributing to drug-induced cardiotoxicity. We analyzed the therapeutic efficacy of selected natural products in HCQ-induced cardiotoxicity through insilico. We selected Syzygium cumini polyphenols, quercetin, and p-coumaric acid. The motivation behind selecting quercetin, and p-coumaric acid is their wide applicability as an antioxidative, anti-inflammatory, antiapoptotic, and cardioprotective.

For predicting quercetin, p-coumaric acid, and HCQ toxicity and physicochemical properties, in silico studies were performed using ProTox II and Swiss ADME. We further performed molecular docking using Autodock Vina and Discovery Studio visualizer to find the affinity of selected polyphenols against signaling molecules and receptors. Then we performed network pharmacological studies of selected signaling molecules.

We analyzed that the computational method indicated quercetin (Δ G -9.3 kcal/mol) has greater binding affinity than p-Coumaric acid for prevention and restoration of the disease while hydroxychloroquine was taken as a control.

It can be concluded that Syzygium cumini, polyphenols may aid in the future therapeutic potential against HCQ-induced cardiotoxicity.