Potential Components of Gedi Leaves (Abelmoschus manihot L. Medik) as XO Enzyme Inhibitors Causing Gout: an in silico Approach

Abstract

Ethnobotanical, the people of Maluku often use gedi leaves as a medicinal ingredient to treat gout, but this has not been done scientifically. Gedi plant has been reported to contain secondary metabolites of flavonoids, steroids, alkaloids, and phenolic compounds with pharmacological activities of anti-inflammatory, anti-oxidant, anti-obesity, analgesic, and anti-diabetic. This research was based on structure-based (molecular docking) using Autodock Tools 4.2, then visualized with Discovery Studio 2016 Client®. While prediction of pharmacokinetic properties, oral administration, and acute oral toxicity with pre-ADMET, Lipinski's rule of five, and ProTox-II. The results showed that the compound myricetin 3-O-β-D-glucopyranoside (a flavonoid component) has the potential to inhibit the xanthine oxidase (XO) enzyme when docked with binding affinity values (ΔG, kcal/mol and Ki, nM) of -10.43; 22.78 compared to allopurinol (-5.46; 98760). Thr1010 and Arg880 were crucial amino acids that play a role when binding. ADME-Tox predictions show good absorption, but not when metabolized in the liver as a drug and mutagenic. In addition, the value of lipophilicity (log P) - 0.053 indicates not good absorption and permeation as a drug candidate, while the LD50 was 1000 mg/kg. Thus, gedi leaves can be gout, but structural modifications are needed.