Design, synthesis, and anti-melanogenic effects of (E)-2-benzoyl-3-(substituted phenyl)acrylonitriles

Abstract

Hwi Young Yun,1 Do Hyun Kim,1 Sujin Son,1 Sultan Ullah,1 Seong Jin Kim,1 Yeon-Jeong Kim,2 Jin-Wook Yoo,1 Yunjin Jung,1 Pusoon Chun,2 Hyung Ryong Moon1 1College of Pharmacy, Pusan National University, Busan, 2College of Pharmacy, Inje University, Gimhae, Republic of Korea Background: Tyrosinase is the most prominent target for inhibitors of hyperpigmentation because it plays a critical role in melaninogenesis. Although many tyrosinase inhibitors have been identified, from both natural and synthetic sources, there remains a considerable demand for novel tyrosinase inhibitors that are safer and more effective. Methods: (E)-2-Benzoyl-3-(substituted phenyl)acrylonitriles (BPA analogs) with a linear β-phenyl-α,β-unsaturated carbonyl scaffold were designed and synthesized as potential tyrosinase inhibitors. We evaluated their effects on cellular tyrosinase activity and melanin biosynthesis in murine B16F10 melanoma cells and their ability to inhibit mushroom tyrosinase activity. Results: BPA analogs exhibited inhibitory activity against mushroom tyrosinase. In particular, BPA13 significantly suppressed melanin biosynthesis and inhibited cellular tyrosinase activity in B16F10 cells in a dose-dependent manner. A docking study revealed that BPA13 had higher binding affinity for tyrosinase than kojic acid. Conclusion: BPA13, which possesses a linear β-phenyl-α,β-unsaturated carbonyl scaffold, is a potential candidate skin-whitening agent and treatment for diseases associated with hyperpigmentation. Keywords: (E)-2-benzoyl-3-(substituted phenyl)acrylonitriles, melanogenesis, tyrosinase inhibitor