An assessment of potential chemoprotectant activity against ricin toxicity by mechanism based glycosidase inhibitors in macrophage J744A.1 cell cultures

The abilities of potential chemoprotectants to inhibit cytotoxicity of ricin have been determined in vitro, using the macrophage cell line J744A.1. Six compounds were tested: α-and β-galactopyranosylamine; N-bromoacetyl-α-d-galactopyranosylamine; N-bromoacetyl-β-D-galactopyranosylamine; N-bromoacetylglucopyranosylamine; and N-bromoacetylmannopyranosylamine. Of the six compounds which were tested, only N-bromoacetyl-α-D-galactopyranosylamine and N-bromoacetyl-β-D-galactopyranosylamine exhibited significant activity against ricin toxicity, as indicated by the release of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). The α-isomer provided greater protection against ricin toxicity and also exhibited less inherent cytotoxicity in the absence of ricin, as compared to the β-isomer. Neither the α-and β-galactopyranosylamines nor the glucose and mannose analogs were promising as potential chemoprotectants.