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 delta-oxa analog of L-ar ginine, have been synthesized and their growth-inhibitory effects eval uated in cultured MIA-PaCa-2 pancreatic carcinoma cells by the (4,5-di methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The r esults indicate that L-canavanine analogs in which the carbon chain-le ngth and/or terminal guanidinooxy functional group has been modified e licit less growth inhibitory activity against these pancreatic cell li nes than L-canavanine. On the other hand, several ester derivatives of L-canavanine have markedly enhanced growth inhibitory activity compar ed 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 agai nst MIA-PaCa-2 cells. (C) 1997 Wiley-Liss, Inc.