Abstract

Research on inhibition of tyrosinase enzyme has attained significant value, because tyrosinase inhibitors have potential applications in medicine, cosmetics (as whitening agents) and in agriculture (as bio­insecticides). Determination and elucidation of new tyrosinase inhibitors are not only beneficial for medical purposes, but their promising applications in improving food quality and nutritional value, controlling insect pests are also crucial. So, it is all time requirement to design novel and more potential inhibitors of tyrosinase enzyme. In this study, considering potent inhibitory activity of polyphenolic compounds against tyrosinase enzyme, a series of Chromane­6,7­diol analogues were designed. All of these designed compounds were subjected to ADME (absorption, distribution, metabolism, and elimination) and extensible toxicity prediction protocol of Accelrys Discovery studio 3.1 client package to predict their molecular properties which are important to be a drug candidate. Subsequently, molecular docking simulations of tyrosinase enzyme with novel designed inhibitors has been the focus of our work. Three distinct algorithms (CDOCKER, LibDock, and AutoDock) are utilized to investigate the binding affinities and conformations of newly designed inhibitors. Most of the compounds fulfilled criterias for ADME and toxicity profile and obtained potential inhibition towards mushroom tyrosinase enzyme. Results obtained through this study suggest that, chromane derivatives with more hydroxyl substitutions produced stronger inhibition by forming extra hydrogen bonds than those with less hydroxyl groups. To be more specific about drug candidate, UM25 obtained as the most potent inhibitor in terms of pharmacokinetic, pharmacodynamics, physicochemical, and docking properties

Authors (3)