Mushroom tyrosinase inhibition by two potent uncompetitive inhibitors.

Two new bi-pyridine compounds, [1,4'] Bipiperidinyl-1'-yl-naphthan-2-yl-methanone (I) and [1,4'] Bipiperidinyl-1'-yl-4-methylphenyl-methane (II) were synthesized and examined for inhibition of the catecholase activity of mushroom tyrosinase in 10 mM phosphate buffer pH 6.8, at 293 K using UV spectrophotometry. Inhibition kinetics indicated that they were uncompetitive inhibitors and the value of the inhibition constants were 5.87 and 1.31 microM for I and II, respectively, which showed high potency. Fluorescent studies confirmed the uncompetitive type of inhibition for these two inhibitors. The inhibition mechanism presumably comes from the presence of a particular hydrophobe site which can accommodate these inhibitors. This site could be formed due to a probable conformational change that was induced by binding of substrate with the enzyme.