pH-dependent inhibition of mushroom tyrosinase by N-substituted N-nitrosohydroxylamines

Figures & data

Figure 1 Effect of pH on mushroom tyrosinase diphenolase activity. The data are shown as relative activity at pH 6.8.

Figure 2 Chemical structures of the N-substituted N-nitrosohydroxylamines tested.

Figure 3 pH-dependence of tyrosinase inhibitory activity for N-substituted N-nitrosohydroxylamines: compound 1(

), 2(

), 4(

), 5 (

) and 6 (

).

Table I.  Inhibition effects of N-substituted N-nitrosohydroxylamines on mushroom tyrosinase at pH6.8 and 5.8.

	IC50 ((μ M)		Type of inhibition
Compound	pH6.8^a	pH5.8	pH6.8^a	pH5.8	PKa
1	0.6	0.075	mixed-II type	non-competitive	5.6
2	2.2	0.26	mixed-II type	competitive	5.9
3	1.1	0.13	competitive	competitive	4.2^b
4	46.0	6.2	mixed-II type	non-competitive	4.1^b
5	13.7	1.1	uncompetitive	mixed-I type	5.7
6	23.8	2.7	uncompetitive	non-competitive	5.7

^a Values have been previously reported [12,13]

^b Reference 21.

Figure 4 Lineweaver-Burk plots of mushroom tyrosinase reaction with compound 2 (A) and 6 (B), at pH 6.8 (a) and 5.8 (b).

Figure 5 Chemical structures of other tyrosinase inhibitors for copper chelation.

Figure 6 Effect of pH on mushroom tyrosinase inhibitory activity for the other HA-type acid inhibitors.

Shiino M, Watanabe Y, Umezawa K. Synthesis of N-substituted N-nitrosohydroxylamines as inhibitors of mushroom tyrosinase. Bioorg Med Chem 2001; 9: 1233–1240

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Shiino M, Watanabe Y, Umezawa K. Synthesis and tyrosinase inhibitory activity of novel N-hydroxybenzyl-N-nitrosohydroxylamines. Bioorg Chem 2003; 31: 129–135

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