Computational study of the potential of phenolic acids berries as an inhibitor of aldose reductase for diabetes mellitus treatment

Abstract

Berries are known to contain bioactive compounds that can function physiologically to optimise health status. One type of bioactive compound found in berries is phenolic acid. Fruits are known to have activities to inhibit aldose reductase (AR). Inhibition of AR can control of microvascular complications of diabetes mellitus, such as blindness, nephropathy and neuropathy. But some AR inhibitors show side effects due to cross-reactions with analogous enzymes, so the purpose of this study is to predict the ability of phenolic acids berries binding to AR and predict selectivity of berries phenolic acids as AR inhibitor through in silico studies. The inhibition activity of twelve berry phenolic acids on AR was analysed using in silico and compared with epalrestat as a commercial AR inhibitor. The phenolic acids were docked to AR using Autodock Vina in PyRx 0.8. 3D molecular interactions visualized using PyMOL were then analyzed with LigPlot+. Chlorogenic acid and neochlorogenic acid show binding energy are higher affinity (-8.0 and -8.3 kcal/mol) than binding energy of epalrestat as a commercial AR inhibitor. The orientation of chlorogenic acid and neochlorogenic acid with the active side of AR showed that the binding of two compounds on the active side of AR occupies the same position as the binding position of epalrestat. Analysis of the interaction of the chlorogenic acid and neochlorogenic acid with AR indicates binding occurs in the pocket specificity of the active side of AR, so indicates that the two compounds have the potential as AR inhibitors.