title: Selective cytotoxicity of azatyrosinamides against ras-transformed NIH 3T3 cells.
abstract: 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.
authors.affiliation: 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
authors.forename: H P
authors.initials: HP
authors.lastname: Wang
authors.forename: T L
authors.initials: TL
authors.lastname: Hwang
authors.forename: On
authors.initials: O
authors.lastname: Lee
authors.forename: Y J
authors.initials: YJ
authors.lastname: Tseng
authors.forename: C Y
authors.initials: CY
authors.lastname: Shu
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: 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
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; C011870:beta-(5-hydroxy-2-pyridyl)alanine; D018631:ras Proteins; D000409:Alanine