Molecular docking studies flavonoid (Quercetin, Isoquercetin, and Kaempferol) of single bulb garlic (Allium sativum) to inhibit lanosterol synthase as antihypercholesterol therapeutic strategies

Abstract

Hypercholesterolemia is the highest risk of CVD which is the biggest disease leading death. One of the Indonesian medicinal plants is single bulb garlic with high flavonoids concentration. Lanosterol synthase, an enzyme on the final stage of cholesterol synthesis are the appropriate inhibition stage for drug. This study aimed to analyze the potential of single bulb garlic flavonoids (quercetin, isoquercetin, and kaempferol) in inhibiting lanosterol synthase. Computational docking analysis was performed using Pyrx, Pymol, Discovery studio, also webserver to predict ADMET and biological activity. Lanosterol synthase was obtained from PDB (PDB ID: IW6J) with RO 48-8071 as native ligand used for control. The results showed binding affinity RO 48-8071 (-10.3 kcal/mol), quercetin (-9.8 kcal/mol), isoquercetin (-6.8 kcal/mol), and kaempferol (-9.9 kcal/mol). Based on interaction and bonding distance, flavonoids have more stable than control. Flavonoids also have potential as APOA1, HMOX1 enhancers, lipid peroxidase inhibitors, cardioprotectant and hepatoprotectant, high distribution volumes, low toxicity, and clearance. This result indicated that quercetin, isoquercetin, and kaempferol from single bulb garlic could be potential ligand to treat hypercholesterolemia, and could proceed to in vitro and in vivo study by improving the absorption.