In Silico Study of Bioactive Compounds from Red Fruit (Pandanus conoideus Lamk.) as Inhibitors of Human Alcohol Dehydrogenase

Abstract

Alcohol addiction and intoxication are serious global health issues, primarily influenced by the metabolic conversion of ethanol into acetaldehyde. This toxic substance causes various harmful effects on the liver, including alcoholic fatty liver (steatosis), steatohepatitis, fibrosis, and hepatocellular carcinoma. Meanwhile, alcohol dehydrogenase (ADH) enzyme facilitates the initial metabolic process. Inhibiting ADH is a potential therapeutic method to slow alcohol metabolism and reduce the side effects of acetaldehyde. Fomepizole is an efficient ADH inhibitor, and the use is limited due to several side effects and high costs, signifying the need to explore safer alternatives. Therefore, this study aimed to investigate the efficacy of bioactive compounds from Pandanus conoideus Lamk. (red fruit), an endemic plant from Papua, Indonesia, as potential ADH inhibitors using in silico methods. Molecular docking simulations and molecular dynamics were used to evaluate the compounds and identify the most promising candidates. Among the compounds evaluated through molecular docking, several flavonoids, such as 3,4',5-trihydroxy-7,3'-dimethoxy flavone (TDF) and taxifolin (TX), had the highest binding affinity scores towards ADH at -7.3 kcal/mol. The next compound producing the highest binding affinity score was quercetin (QE), with a value of -7.1 kcal/mol. Molecular dynamics simulations lasting more than 50 ns signified that QE was the most stable ligand, with root-mean-square deviation (RMSD) value that remained below 5 Å. The results generally showed that only QE from Pandanus conoideus had potential as ADH inhibitor.

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