A general method for tritium labelling of benzimidazole carbamates by catalytic exchange in dioxane solutions

Abstract

AbstractBenzimidazole carbamates (BZCs) act as inhibitors of the tubulin‐microtubule equilibria in eukaryotic organisms. Recently drug resistance to this class of compounds in helminth parasites has been shown to be due to a reduced ability of resistant tubulin to bind BZCs. In order to quantitate the nature of the tubulin‐BZC interaction a general method for the specific tritium labelling of BZCs has been developed. The BZCs: mebendazole, oxfendazole, parbendazole, oxibendazole, albendazole and fenbendazole were labelled by catalytic exchange using palladium on calcium carbonate in pure dioxane at 60°C under tritium gas. The position of label incorporation for tritiated albendazole was determined by tritium‐NMR as the 4‐position of benzimidazole nucleus. The yields for individual BZCs varied from 8 to 68% for a range of specific activity of 0.44 to 13.4 Ci/mmole.