Synthesis and bioactivity of novel isoxazole chalcone derivatives on tyrosinase and melanin synthesis in murine B16 cells for the treatment of vitiligo.

Abstract A new series of chalcone derivatives 1 – 18 , bearing isoxazole moieties were designed and synthesized, and biologically evaluated for their activity on mushroom tyrosinase and melanin synthesis in murine B16 cells. The result indicated that most of prepared compounds 1 – 18 showed potent activating effect on tyrosinase, especially for 1 – 2 , 4 , 6 – 7 , 9 and 15 . Among them, compounds 2 , 4 and 9 demonstrated the best activity with EC 50  = 1.3, 2.5 and 3.0 μmol·L −1 respectively, much better than the positive control 8-methoxypsoralan (8-MOP, EC 50  = 14.8 μmol·L −1 ); In B16 cells, all the tested compounds exhibited a stronger activity on melanogenesis than 8-MOP (with the value of 115%). It was interesting that derivatives substituted with halogen ( 1 , 2 , 4 , 5 , 7 , 9 ) were generally more potent. Compounds 2 (463%) and 18 (438%) with 3 and 4-fold potency compared with 8-MOP respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo.