Castanospermine, a tetrahydroxylated alkaloid that inhibits beta-glucosidase and beta-glucocerebrosidase.
Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) was tested against a variety of commercially available glycosidases and found to be a potent inhibitor of almond emulsin beta-glucosidase, and also to inhibit fungal beta-xylosidase. This alkaloid was inactive on yeast alpha-glucosidase, alpha- or beta-galactosidase, alpha-mannosidase, beta-N-acetylhexosaminidase, beta-glucuronidase, alpha-L-fucosidase. Fifty-percent inhibition of beta-glucosidase required about 10 micrograms/ml of castanospermine. The amount of inhibition was uniform throughout the time course, and the inhibition with regard to substrate concentration (p-nitrophenyl-beta-D-glucopyranoside) appeared to be of the mixed type. Castanospermine was also a potent inhibitor of beta-glucocerebrosidase when assayed with fibroblast extracts using either a fluorimetric or a radioactive assay. Interestingly enough, castanospermine also inhibited the lysosomal alpha-glucosidase, and this inhibition required comparable levels of alkaloid to that required for inhibition of beta-glucocerebrosidase. However, a number of other lysosomal glycosidases were not sensitive to castanospermine (i.e., alpha- or beta-galactosidase, alpha- or beta-mannosidase, alpha- or beta-L-fucosidase, beta-N-acetylhexosaminidase, beta-glucuronidase).
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D007212:Indolizines; D010944:Plants; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*; D054836:Indolizidines
D000470:Alkaloids; D005959:Glucosidases; D005962:Glucosylceramidase; D006026:Glycoside Hydrolases; D007212:Indolizines; D001617:beta-Glucosidase; C037806:castanospermine; D054836:Indolizidines