Design of diazo dyes based on 2, 6-diamino-4- chloropyrimidine compound and the analysis of their interaction with tyrosinase using molecular docking method

Tyrosinase is a copper-containing enzyme which belongs to the oxidasesuperfamily protein. This enzyme catalyzes the main reaction of melanin biosynthesis; however, its abnormal accumulation is responsible for hyperpigmentation related disorders like senile lentigines, freckles, melasma and other forms of melanin hyperpigmentation which causes serious esthetic problems. The reactions catalyzed by this enzyme, the hydroxylation of a monophenol and the conversion of an ο-diphenol to the corresponding o-quinone lead to melanin production which plays a vital protective role against skin photocarcinogenesis, and hence knowledge of tyrosinase catalytic mechanisms and regulation may have medical, cosmetic and agriculture application.Numerous efforts have so far been made to develop new tyrosinase inhibitors around the world and various synthetic chemical compounds have been nominated. Two novel compounds based on 2 ,6-diamino-4-chloropyrimidine were synthesized and evaluated as tyrosinase inhibitors. In order to know the binding of the synthesized compounds, molecular docking studies of the compound were carried out against tyrosinase enzyme and make it possible to gain a better understanding of the tyrosinase inhibition mechanism. The chemical structure of all compounds was designed using the chemdrawprogramand then subjectedinto Hyperchem software for energy minimization.Themushroom tyrosinase (PDBID 2Y9X) was dockedby Autodock 4.2 program with synthesized compounds. The structure of the compounds was confirmed by FT-IR, H NMR, and C NMR spectroscopic techniques. We simulation the docking between tyrosinase and compounds, and results suggested that these compounds inhibit tyrosinase activity, and this result confirmed by tyrosinase assay in experimental methods.

کلیدواژه ها:

Tyrosinase ، Molecular docking ، Inhibitors ، 2 ، 6-diamino-4-chloropyrimidine