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



(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.



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.



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.
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Hwi Young
HY
Yun
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Do Hyun
DH
Kim
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Sujin
S
Son
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Sultan
S
Ullah
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Seong Jin
SJ
Kim
College of Pharmacy, Inje University, Gimhae, Republic of Korea.
Yeon-Jeong
YJ
Kim
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Jin-Wook
JW
Yoo
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Yunjin
Y
Jung
College of Pharmacy, Inje University, Gimhae, Republic of Korea.
Pusoon
P
Chun
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Hyung Ryong
HR
Moon
D000181:Acrylonitrile / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000363:Agaricales / Q000201:enzymology; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000201:enzymology; D051379:Mice; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011753:Pyrones / Q000378:metabolism; D062327:Skin Lightening Preparations / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D012880:Skin Pigmentation / Q000187:drug effects*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D008543:Melanins; D011753:Pyrones; D062327:Skin Lightening Preparations; C011890:kojic acid; D014442:Monophenol Monooxygenase; D000181:Acrylonitrile
(E)-2-benzoyl-3-(substituted phenyl)acrylonitriles; melanogenesis; tyrosinase inhibitor