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Synthesis and structure‐activity studies of some antitumor congeners of L‐canavanine
Author(s) -
Phuket Supinan R. Na,
Trifonov Latchezar S.,
Crooks Peter A.,
Rosenthal Gerald A.,
Freeman James W.,
Strodel William E.
Publication year - 1997
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199704)40:4<325::aid-ddr6>3.0.co;2-l
Subject(s) - canavanine , arginine , chemistry , cell culture , biochemistry , stereochemistry , bromide , cell growth , inhibitory postsynaptic potential , amino acid , biology , endocrinology , organic chemistry , genetics
A number of structural analogs of the antitumor compound, L‐canavanine, [L‐2‐amino‐4‐(guanidinooxy)butyric acid], a δ‐oxa analog of L‐arginine, have been synthesized and their growth‐inhibitory effects evaluated in cultured MIA‐PaCa‐2 pancreatic carcinoma cells by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results indicate that L‐canavanine analogs in which the carbon chain‐length and/or terminal guanidinooxy functional group has been modified elicit less growth inhibitory activity against these pancreatic cell lines than L‐canavanine. On the other hand, several ester derivatives of L‐canavanine have markedly enhanced growth inhibitory activity compared to L‐canavanine. Thus, esterification of the carboxylic acid group constitutes an effective structural modification, which significantly amplifies the growth inhibitory properties of the parent compound against MIA‐PaCa‐2 cells. Drug Dev. Res. 40:325–332, 1997. © 1997 Wiley‐Liss, Inc.