Synthesis and structure-activity studies of some antitumor congeners of L-canavanine

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.