Selective cytotoxicity of azatyrosinamides against ras-transformed NIH 3T3 cells

H P Wang; T L Hwang; On Lee; Y J Tseng; C Y Shu; S J Lee

doi:10.1016/j.bmcl.2005.06.048

Selective cytotoxicity of azatyrosinamides against ras-transformed NIH 3T3 cells

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4272-4. doi: 10.1016/j.bmcl.2005.06.048.

Authors

H P Wang¹, T L Hwang, On Lee, Y J Tseng, C Y Shu, S J Lee

Affiliation

¹ 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

PMID: 16039850
DOI: 10.1016/j.bmcl.2005.06.048

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alanine / analogs & derivatives
Alanine / chemical synthesis
Alanine / pharmacology
Amides
Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Apoptosis / drug effects*
Cell Line, Transformed
Inhibitory Concentration 50
Mice
NIH 3T3 Cells
Structure-Activity Relationship
ras Proteins

Substances

Amides
Antineoplastic Agents
beta-(5-hydroxy-2-pyridyl)alanine
ras Proteins
Alanine