Searching for indole derivatives as potential mushroom tyrosinase inhibitors

Figures & data

Figure 1. Chemical structure of INSTIs.

Scheme 1. Reagents and conditions: (i) POCl₃, CH₃CON(CH₃)₂, RT, 12 h; (ii) benzyl bromide or chloride, NaH, DMF, mw: 10 min at continuous temperature (50 °C), 100 W; (iii) diethyl oxalate, dry CH₃ONa, THF, two separate steps under the same conditions mw: 2 min, at continuous temperature (50 °C), 250 W and (iv) 2 N NaOH, MeOH, RT, 1.5 h.

Figure 2. Chemical structure of Kojic acid, CHI 1043 and its analogs.

Table 1. Inhibitory activity against mushroom tyrosinase of indole derivatives.

Compound	IC50
Kojic acid	17.76 ± 0.18 µM*
CHI1043	312 ± 1.92 µM*
1	NI^a µM
2	>400
3	NI^a
4	224 ± 1.23 µM*
5	NI^a
6	NI^a
7	372 ± 1.87 µM

^aNo obvious inhibition at 500 μM (< 20%).

*p< 0.05.

Figure 3. New potential indole tyrosinase inhibitors (ITIs).

Scheme 2. Reagents and conditions: (i) oxalyl chloride, dry Et₂O, N₂, 0 °C, 3 h; (ii) NH₂-Het, dry THF, N₂, rt, 1.5 h and (iii) 4-fluorobenzyl bromide, t-BuOK, THF, rt, 2 h.

Scheme 3. Reagents and conditions: (i) thionyl chloride, Δ, 2 h; (ii) Et₂AlCl, CH₂Cl₂, 0 °C, 2 h; (iii) 4-fluorobenzyl bromide, t-BuOK, THF, rt, 2 h and (iv) BBr₃ 1 M sol. in CH₂Cl₂, CH₂Cl₂, rt, 16 h.

Figure 4. Lineweaver–Burk plots for the inhibition of tyrosinase respect to l-DOPA as substrate in the presence of CHI 1043 (a) and 4 (b).