title: (E)-2-Cyano-3-(substituted phenyl)acrylamide analogs as potent inhibitors of tyrosinase: A linear β-phenyl-α,β-unsaturated carbonyl scaffold.
abstract: In this study, we synthesized (E)-2-cyano-3-(substituted phenyl)acrylamide (CPA) derivatives which possess a linear β-phenyl-α,β-unsaturated carbonyl scaffold and examined their inhibitory activities against tyrosinase. CPA analogs exerted inhibitory activity against mushroom tyrosinase. Results from the docking simulation indicated that CPA2 could bind directly to the active site of mushroom tyrosinase and the binding affinity of CPA2 for tyrosinase might be higher than that of kojic acid, a well-known potent tyrosinase inhibitor. In B16F10 cells, CPA2 significantly suppressed tyrosinase activity and melanogenesis in a dose-dependent manner. At the concentration of 25μM, CPA2 exhibited tyrosinase inhibitory activity comparable to that of kojic acid with no cytotoxic effect. Results from the present study suggest that CPA2 bearing a linear β-phenyl-α,β-unsaturated carbonyl scaffold may be the potential candidate for treatment of diseases associated with hyperpigmentation and that a linear β-phenyl-α,β-unsaturated carbonyl scaffold might be closely related to potent tyrosinase inhibition.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Son
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Haewon
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Sultan
authors.initials: S
authors.lastname: Ullah
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Inje University, 197 Inje-ro, Gimhae, Gyeongnam 621-749, Republic of Korea.
authors.forename: Yeon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Yoo
authors.affiliation: College of Pharmacy, Inje University, 197 Inje-ro, Gimhae, Gyeongnam 621-749, Republic of Korea. Electronic address: pusoon@inje.ac.kr.
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: mhr108@pusan.ac.kr.
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
mesh_terms: D020106:Acrylamide / Q000737:chemistry* / Q000494:pharmacology*; D000363:Agaricales / Q000201:enzymology; D000818:Animals; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008543:Melanins / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008543:Melanins; D020106:Acrylamide; D014442:Monophenol Monooxygenase
keywords: (E)-2-Cyano-3-(substituted phenyl)acrylamide; Melanogenesis; Tyrosinase inhibitor