title: (Z)-2-(Benzo[d]thiazol-2-ylamino)-5-(substituted benzylidene)thiazol-4(5H)-one Derivatives as Novel Tyrosinase Inhibitors.
abstract: Inhibiting tyrosinase is an important goal to prevent melanin accumulation in skin and thereby to inhibit pigmentation disorders. Therefore, tyrosinase inhibitors are an attractive target in cosmetics and treatments for pigmentation disorders. However, only a few tyrosinase inhibitors are currently available because of their toxic effects to skin or lack of selectivity and stability. Here, we newly synthesized thirteen (Z)-2-(benzo[d]thiazol-2-ylamino)-5-(substituted benzylidene)thiazol-4(5H)-one derivatives and examined their effect on melanogenesis. Of these compounds, MHY2081 had the strongest inhibitory effect on tyrosinase without cytotoxicity in B16F10 melanoma cells. Consistently, melanogenesis was notably decreased by MHY2081 treatment. As an underlying mechanism, docking simulation showed that compared to kojic acid, a well-known competitive tyrosinase inhibitor which forms a hydrogen bond and aromatic interaction with tyrosinase, MHY2081 has stronger affinity with tyrosinase by forming three hydrogen bonds and a hydrophobic interaction with residues of tyrosinase. In parallel with this, Lineweaver-Burk plot analysis showed that MHY2081 is a strong competitive inhibitor of tyrosinase. In conclusion, MHY2081 may be a novel tyrosinase inhibitor for prevention and treatment of pigmentation disorders.
authors.affiliation: College of Pharmacy, Pusan National University.
authors.forename: Kyeong Ha
authors.initials: KH
authors.lastname: Kang
authors.forename: Bonggi
authors.initials: B
authors.lastname: Lee
authors.forename: Sujin
authors.initials: S
authors.lastname: Son
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Yun
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Moon
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jeong
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental; D051379:Mice; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010859:Pigmentation Disorders / Q000188:drug therapy / Q000378:metabolism*; D012867:Skin / Q000201:enzymology* / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects*; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D008543:Melanins; D013844:Thiazoles; D014442:Monophenol Monooxygenase