Preparation and antitumor activities of β-azatyrosinamides

Authors

H.-P.O. Wang
M.-F. Wu
C.-Y. Shu
O. Lee
S.-J. Lee
C.-H. Sung

Abstract

A large number of human prostate cancer cases has been proven to be genetically associated with ras-mutation. A series of α-azatyrosinamides prepared in this laboratory demonstrated selective cytotoxicity against rasmutated NIH3T3 cells while with little toxicity on wild type NIH3T3 cells. The compounds also proved to be active in inhibiting human prostate cancer cell lines. Using α-azatyrosinamides as the leads, we prepared another series of novel β-azatyrosinamides for the purpose of treating human prostate cancer. Preparation of the β-azatyrosinamides starts from 5-benzyloxypyridin-2-ylaldehyde (1), which upon reaction with malonic acid and ammonium acetate afforded 5-benzyloxy-β-azatyrosine (2). This intermediate was allowed to react with benzyloxycarbonic anhydride followed by coupling with a variety of amines to form the desired β-azatyrosinamides 4-15. The compounds exhibited an inhibitory effect on the growth of ras-mutated NIH3T3 cells with IC50 ranged between 0.13 ± 0.01 mM and 3.16 ± 1.45 mM, which were with activities 2-57 fold higher than that of azatyrosine, but were much less active than their α-amino acid analogues. The selective toxicity, in terms of the ratio of IC50 against wild type NIH3T3 to that against ras-transformed NIH3T3 cell lines, is at the range of 0.7-11.9. The IC50's of β-azatyrosinamides 4-15 on PC-3 human prostate cancer cell line ranged between 0.15 ± 0.02 mM and 13.05 ± 9.41 mM, which were 0.4-33 fold lower than that of azatyrosine.

Recommended Citation

Wang, H.-P.O.; Wu, M.-F.; Shu, C.-Y.; Lee, O.; Lee, S.-J.; and Sung, C.-H. (2000) "Preparation and antitumor activities of β-azatyrosinamides," Journal of Food and Drug Analysis: Vol. 8 : Iss. 3 , Article 5.
Available at: https://doi.org/10.38212/2224-6614.2833

Fulltext URL

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