Structure-activity relationship of naphthaldehydethiosemicarbazones in melanogenesis inhibition.
2-(Naphthalen-1-ylmethylene)hydrazinecarbothioamide (14, IC(50)=1.1μM) was discovered as a highly potent inhibitor of melanogenesis. To define the role of hydrogens (at N1 and N3) and sulfur in 14, a series of analogs 15a-p were synthesized and evaluated for anti-melanogenic activity using melanoma B16 cells under the stimulus of α-MSH. It was observed that replacement of either of these hydrogens at N1 or N3 by substituents increases the activity significantly. Conversely, concomitant substitutions decrease the inhibitory potency. In addition, the presence of sulfur in thiosemicarbazone is essential for the activity.
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Pillaiyar
P
Thanigaimalai
Eeda Venkateswara
EV
Rao
Ki-Cheul
KC
Lee
Vinay K
VK
Sharma
Eunmiri
E
Roh
Youngsoo
Y
Kim
Sang-Hun
SH
Jung
D045744:Cell Line, Tumor; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D015394:Molecular Structure; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008543:Melanins; D012663:Semicarbazides; D000521:alpha-MSH