Département de chimie moléculaire

Tyrosinase (Ty) is a copper-contg. enzyme widely present in plants, bacteria, and humans, where it is involved in biosynthesis of melanin-type pigments. Development of Ty inhibitors is an important approach to control the prodn. and the accumulation of pigments in living systems. In this paper, we focused our interest in phenylthiourea (PTU) and phenylmethylene thiosemicarbazone (PTSC) recognized as inhibitors of tyrosinase by combining enzymic studies and coordination chem. methods. Both are efficient inhibitors of mushroom tyrosinase and they can be considered mainly as competitive inhibitors. Computational studies verify that PTSC and PTU inhibitors interact with the metal center of the active site. The KIC value of 0.93 $μ$M confirms that PTSC is a much more efficient inhibitor than PTU, for which a KIC value of 58 $μ$M was detd. The estn. of the binding free energies inhibitors/Ty confirms the high inhibitor efficiency of PTSC. Binding studies of PTSC along with PTU to a dinuclear copper(II) complex ([Cu2($μ$-BPMP)($μ$-OH)](ClO4)2 (1); H-BPMP = 2,6-bis-[bis(2-pyridylmethyl)aminomethyl]-4-methylphenol) known to be a structural and functional model for the tyrosinase catecholase activity, have been performed. Interactions of the compds. with the dicopper model complex 1 were followed by spectrophotometry and electrospray ionization (ESI). The mol. structure of 1-PTSC and 1-PTU adducts were detd. by single-crystal X-ray diffraction anal. showing for both an unusual bridging binding mode on the dicopper center. These results reflect their adaptable binding mode in relation to the geometry and chelate size of the dicopper center. [on SciFinder(R)]