title: Identification of a potent and noncytotoxic inhibitor of melanin production.
abstract: On the basis of a hit from random screening, biaryl amide derivatives were prepared in a combinatorial manner via parallel solution-phase synthesis, and their effects on melanocytes were investigated to discover new effective skin depigmenting agents. Among the 120 derivatives prepared, five members exhibited a >30% reduction of melanin production at 30 microM with a cell viability of >90%. In particular, compound A(3)/B(5) exhibited effective inhibitory activity on melanin synthesis. Although the inhibition percentage of A(3)/B(5) was slightly lower than that of the positive reference compound, phenylthiourea (PTU), A(3)/B(5) demonstrated a much better cell viability than PTU. In vivo evaluation of A(3)/B(5) also showed a significant decrease of melanin pigments. In addition, the in silico classification model was built based on the experimental data of library members. Our results suggest that these biaryl amide derivatives may act as potent skin depigmenting agents.
authors.affiliation: College of Pharmacy, Seoul National University, San 56-1, Shilim, Kwanak, Seoul 151-742, Republic of Korea.
authors.forename: Soonho
authors.initials: S
authors.lastname: Hwang
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Choi
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Shinae
authors.initials: S
authors.lastname: Kim
authors.forename: Jinkyung
authors.initials: J
authors.lastname: In
authors.forename: Sang Keun
authors.initials: SK
authors.lastname: Ha
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D006168:Guinea Pigs; D008543:Melanins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects; D051379:Mice; D010670:Phenylthiourea / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
chemical_list: D000577:Amides; D001549:Benzamides; D008543:Melanins; C553150:N-(3,5-dimethylphenyl)-3-methoxybenzamide; D010670:Phenylthiourea