Selective cytotoxicity of azatyrosinamides against ras-transformed NIH 3T3 cells.
This study aims to develop novel azatyrosinamide compounds structurally modified from ras-specific antioncogenic azatyrosine. Analogues 4-15 were prepared and their inhibition on the growth of wild-type and ras-transformed NIH 3T3 cell lines was compared. Compound 12 was found to be the most active with IC50 16.5+/-2.2 microM which is 458-fold more potent than that of azatyrosine. The selective toxicity, defined as IC(50 wild-type)/IC(50 ras-transformed) for this compound was 138.5.
Wang
H P
HP
Graduate Institute of Natural Products, Chang Gung University College of Medicine, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan. hpw@mail.cgu.edu.tw
Hwang
T L
TL
Lee
On
O
Tseng
Y J
YJ
Shu
C Y
CY
Lee
S J
SJ
D000409:Alanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D000577:Amides; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002461:Cell Line, Transformed; D020128:Inhibitory Concentration 50; D051379:Mice; D041681:NIH 3T3 Cells; D013329:Structure-Activity Relationship; D018631:ras Proteins
D000577:Amides; D000970:Antineoplastic Agents; C011870:beta-(5-hydroxy-2-pyridyl)alanine; D018631:ras Proteins; D000409:Alanine