Synthesis of diazo dyes from 2, 6-diamino-4- chloropyrimidine compound and the biological evaluation of their effects on tyrosinase activity

Tyrosinase is a membrane bound copper-containing glycoprotein andthe binuclear center together with three specific histidine residues forms a square-pyramidal structure. In melanocytic cells biosynthesis of melanin regulated by tyrosinase. In mammals tyrosinase oxidizeLtyrosine todopaquinone through L-3,4-dihydorxyphenylalanine (L-DOPA). Thenthrough several reactions Dopaquinone change into brown to black melanin. Melanin determines the colorof human skin, hair, and eyes. Various skin disorders result in the accumulation of an excessive level of epidermal pigmentation. Thus, inhibiting the formation of melanin may result in a reduction in skin darkness. Numerous efforts have so far been made to develop new tyrosinase inhibitors around the world and various chemical or naturalcompounds have been nominated.Two novel compounds based on 2,6-diamino-4-chloropyrimidine were synthesized and evaluated as tyrosinase inhibitors. In tyrosinase assay LDOPA was used as the substrate for diphenolase activity. The reaction media for enzyme activity assay contained LDOPA and mushroom tyrosinase in sodium phosphate buffer (pH 6.8) and different concentrations (10-100μM) of inhibitors. Theabsorbance was taken at 490 nm. The structures of the compounds were confirmed by FT-IR, H NMR and C NMR spectroscopic techniques. Compounds a and bbased on 2,6-diamino-4-chloropyrimidin exhibited inhibitory potential with IC50 values 24.25 μM and 29.74 μM, respectively, as compared with standard kojicacid.Thecompounds showed potent inhibitory potentialsagainst mushroom tyrosinase

کلیدواژه ها:

Tyrosinase ، L-DOPA ، Melanin ، 2 ، 6-diamino-4-chloropyrimidine ، Inhibitor