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: alpha- and beta-galactopyranosylamine; N-bromoacetyl-alpha-D-galactopyranosylamine; N-bromoacetyl-beta-D-galactopyranosylamine; N-bromoacetylglucopyranosylamine; and N-bromoacetylmannopyranosylamine. Of the six compounds which were tested, only N-bromoacetyl-alpha-D-galactopyranosylamine and N-bromoacetyl-beta-D-galactopyranosylamine exhibited significant activity against ricin toxicity, as indicated by the release of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). The alpha-isomer provided greater protection against ricin toxicity and also exhibited less inherent cytotoxicity in the absence of ricin, as compared to the beta-isomer. Neither the alpha- and beta-galactopyranosylamines nor the glucose and mannose analogs were promising as potential chemoprotectants.
Hassoun
E A
EA
Department of Pharmaceutical Sciences, Creighton University Health Sciences Center, Omaha, NE 68178.
Bagchi
D
D
Roche
V F
VF
Stohs
S J
SJ
D001219:Aspartate Aminotransferases / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology*; D012276:Ricin / Q000037:antagonists & inhibitors*
D003470:Culture Media; D007202:Indicators and Reagents; D012276:Ricin; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D006026:Glycoside Hydrolases