Molecular Docking and Dynamics Study of Compounds from Combretum indicum var. B Seeds as Alcohol Dehydrogenase Inhibitors

Abstract

Ethylene glycol is one of the causes of acute kidney failure due to the metabolic byproducts produced on its metabolism by the enzyme alcohol dehydrogenase (ADH) in the liver. Therefore, this study is aimed at identifying potential compounds from Combretum indicum var B seeds that can inhibit ADH enzyme. The seeds of Combretum indicum var B were extracted by maceration in ethanol, the constituents of the extract was analysed by LC-MS (Liquid Chromatography-Mass Spectrometry). The alcohol dehydrogenase inhibitory activity of the identified compounds was investigated in silico via molecular docking and dynamics study. Their potential for oral use was also investigated using the SwissADME and admetSAR software. The results of the LC-MS analysis identified seventeen (17) compounds in the seeds of Combretum indicum. The molecular docking and dynamics results showed that six (6) of the compounds, namely; 9,10-Dihydrophenanthrene, 2,3-Dihydroxy-3',4,4',5-tetramethoxybibenzyl, 2-Hydroxy-3,4,6,7-tetramethoxy-9,10-dihydro phenanthrene, 3-Hydroxy-2,4,6,7-tetramethoxy-9,10 dihydrophenanthrene, Erythrophyllic acid, and 3'-Hydroxy-3,4,4'5-tetramethoxystilbene has high binding energy. These compounds exhibited better binding energy than the standard ligand (fomepizole) - a known inhibitor of ADH. Therefore, these compounds could serve as potential inhibitors of alcohol dehydrogenase with better activity than the standard ligand.