Structural characteristics of thiosemicarbazones as inhibitors of melanogenesis.
A series of thiosemicarbazones 2(e-s) have been synthesized and studied their structure-activity relationship as melanogenesis inhibitor. Among them, (Z)-2-(naphthalen-1-ylmethylene)hydrazinecarbothioamide (2q, >100% inhibition at 10 μM, IC(50)=1.1 μM, ClogP=3.039) showed the strongest inhibitory activity. Regarding their structure-activity relationship, the hydrophobic substituents regardless the position on phenyl ring of benzaldehyde thiosemicarbazones enhance the inhibitory activity. Furthermore, the aromatic group of benzaldehydethiosemicarbazones can be replaced with sterically bulky cyclohexyl. Thus, hydrophobicity of the aryl or alkyl group on hydrazine of thiosemicarbazones is determinant factor for their inhibitory activity in melanogenesis rather than planarity.
Lee
Ki-Cheul
KC
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Thanigaimalai
Pillaiyar
P
Sharma
Vinay K
VK
Kim
Min-Seok
MS
Roh
Eunmiri
E
Hwang
Bang-Yeon
BY
Kim
Youngsoo
Y
Jung
Sang-Hun
SH
D000818:Animals; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology*
D008543:Melanins; D013882:Thiosemicarbazones