Synthesis and bioactivity of novel isoxazole chalcone derivatives on tyrosinase and melanin synthesis in murine B16 cells for the treatment of vitiligo.
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 EC50=1.3, 2.5 and 3.0μmol·L-1respectively, much better than the positive control 8-methoxypsoralan (8-MOP, EC50=14.8μmol·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.
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
Chao
C
Niu
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China.
Li
L
Yin
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
Li Fei
LF
Nie
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China.
Jun
J
Dou
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
Jiang Yu
JY
Zhao
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
Gen
G
Li
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China. Electronic address: haji@ms.xjb.ac.cn.
Haji Akber
HA
Aisa
D000363:Agaricales / Q000201:enzymology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014820:Vitiligo / Q000188:drug therapy*
D007555:Isoxazoles; D008543:Melanins; D002599:Chalcone; D014442:Monophenol Monooxygenase
Chalcone; Melanin synthesis; SAR; Tyrosinase; Vitiligo