engleski

Synthesis of glucoconjugates with heterocyclic oximes

The heterocyclic parts of these conjugates were quinuclidinium, pyridinium or imidazolium oximes, basic structures of many compounds tested in vitro and in vivo as antidotes in poisoning by organophosphorus (OP) compounds such as pesticides and nerve warfare agents. The OP compounds inhibit the enzyme acetylcholinesterase (AChE), essentially irreversibly. This causes accumulation of acetylcholine (ACh) which is responsible for many toxic effects. An oxime is considered to be an efficient antidote if it has a high reactivation rate constant and if it persists in blood circulation for a long enough period of time. Its toxicity should be low as well. The glucoconjugates on which we report in this work were designed as possible model compounds satisfying these requirements. It was previously found that attachment of a sugar moiety to the oxime derivatives increases the bioavailability of the antidote. Thus, we presume that the sugar moiety might be recognized by sites responsible for sugar transport trough the cell membrane leading to the increased permeability of membranes for the quaternary oximes. Furthermore, the previously reported glucoconjugates were less toxic than non-sugar conjugates, and some of them also displayed higher efficacy.

glucoconjugates; oximes

Toxicology 233 (2007) (1-3) 227-228.