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 EC50=1.3, 2.5 and 3.0μmol·L-1 respectively, 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.

• Authors: Chao Niu, Li Yin, Li Fei Nie, Jun Dou, Jiang Yu Zhao, Gen Li, Haji Akber Aisa
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 24 Issue 21 Pg. 5440-5448 (11 01 2016) ISSN: 1464-3391 [Electronic] England
• PMID: 27622747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Isoxazoles
• Melanins
• Chalcone
• Monophenol Monooxygenase

Topics

• Agaricales (enzymology)
• Animals
• Cell Survival (drug effects)
• Chalcone (analogs & derivatives, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Isoxazoles (chemical synthesis, chemistry, pharmacology)
• Melanins (biosynthesis)
• Mice
• Molecular Structure
• Monophenol Monooxygenase (biosynthesis)
• Structure-Activity Relationship
• Tumor Cells, Cultured
• Vitiligo (drug therapy)