Synthesis of N-(substituted phenyl)-D-xylopyranosylamines as potential modifiers of the formation of glycosaminoglycans

Abstract

N-(Substituted-phenyl)-D-xylopyranosylamines and their O-peracetyl derivatives have been synthesized and tested for their ability (a) to inhibit the replication of cultured B16 melanoma cells and (b) to modify the synthesis of glycosaminoglycans by these neoplastic cells. The most cytotoxic compound synthesized was N-(p-methoxyphenyl)-D-xylopyranosylamine (6), which produced 50% inhibition of cellular proliferation at a concentration of 2 microM; a number of other compounds were relatively cytotoxic, causing 50% inhibition of cell replication at levels of 12 to 25 microM. Several of the synthesized xylosides appeared to be capable of serving as artificial initiators of glycosaminoglycan synthesis, with the most active agents causing approximately 2- to 4-fold increases in the incorporation of [35S]sulfate into the glycosaminoglycans of B16 melanoma cells excreted into the culture medium.