Functionality study of chalcone-hydroxypyridinone hybrids as tyrosinase inhibitors and influence on anti-tyrosinase activity

Figures & data

Figure 1. Structure of a typical chalcone and designed molecules 1.

Scheme 1. Synthetic route of compounds 1. Reagents and conditions: (i) BnCl, NaOH, MeOH/H₂O, 70 °C, 6 h, 80% yield; (ii) appropriate amines, EtOH, reflux, overnight, (iii) MnO₂, 1,4-dioxane, (iv) Br₂, CHCl₃, rt, 10 min; (v) PPh₃, CH₂Cl₂, 30 min, (vi) tert-BuOK, dry THF, (vii) BBr₃, DCM, 0 °C to rt, 2 h, 55–72% yield.

Figure 2. Inhibitory effect of 1a, 1d, 1f, and 1n on the monophenolase activity of mushroom tyrosinase. The assays were performed at 30 °C and pH 6.8.

Table 1. Inhibition of compounds (1a–1o) (50 µM) on monophenolase activity of mushroom tyrosinase under the conditions of 30 °C and pH 6.8.

Compounds	Inhibition (%)	R^2	X	clogP^a
1a	85.3	4-F	NCH3	1.60
1b	66.7	2-OH, 4-OCH3	NCH3	1.41
1c	50.3	2,4-dimethoxy	O	1.51
1d	89.5	4-F	NH	1.53
1e	63.3	H	NC2H5	1.81
1f	78.8	3,4-dihydroxyl	NC2H5	0.84
1g	71.4	2-OH, 4-OCH3	NC2H5	1.78
1h	57.8	4-F	NC2H5	1.97
1i	72.8	H	NCH3	1.43
1j	69.4	3,4-dihydroxyl	NC4H9	2.31
1k	64.6	2-OH, 4-OCH3	NC4H9	2.84
1l	50.3	4-F	NC4H9	3.03
1m	66.7	H	NH	1.36
1n	87.6	3,4-dimethoxy	NH	1.01
1o	63.3	2-OH, 4-OCH3	NH	1.34
Kojic acid	75.4	–	–	−0.89

^a The clogP values were calculated from website: http://www.molinspiration.com/cgi-bin/properties.

Figure 3. Inhibitory effect of different concentrations of 1a (a) and 1d (b) on the diphenolase activity of tyrosinase. The assays were performed at 30 °C and pH 6.8.

Figure 4. Determination of the inhibitory reversibility of 1a (a) and 1d (b) on mushroom tyrosinase. The concentrations of inhibitors for curves were 0.00, 3.125, 6.25, 12.5, and 25.00 µM, respectively. The assays were performed at 30 °C and pH 6.8.

Figure 5. Speciation plots of copper ion in the presence of 1n.

Scheme 2. Proton equilibria and resonance structure of 1n.

Figure 6. Configuration for the interaction of compound 1d with tyrosinase.