TY - JOUR
T1 - Sugar conjugates of pyridinium aldoximes as antidotes against organophosphate poisoning
AU - Heldman, Eli
AU - Ashani, Yacov
AU - Raveh, Lily
AU - Rachaman, Eliezer S.
N1 - Funding Information:
This work was supported by a grant (DAJA 37-80-C-0187)fr om the U.S. Army through its European office. We thank Drs. Bernard Green and Harold M. Flowers for useful discussion.W e are also grateful to Mrs. Rita’ Sahar and Mr. Joseph Alfasi for their skillful technicala ssistance.
PY - 1986/8/15
Y1 - 1986/8/15
N2 - A series of pyridinium aldoximes having a sugar conjugated to the pyridine ring has been prepared as potential antidotes against organophosphate poisoning. The sugar residue was attached either directly through C-1 or C-6 of the pyranose ring or through a C3 bridge between the glycosyl group and the nitrogen atom of the pyridine moiety. Attachment of a sugar group to the oxime derivative seems to increase the bioavailability of the antidote. The clearance rate of the sugar conjugates was significantly lower than that of their non-sugar analogs and thus they were retained longer in the blood circulation. The sugar derivatives were more potent in decreasing paraoxon-induced hypothermia (which is regulated within the central nervous system) than N-methyl-2-pyridiniumaldoxime methanesulfonate, one of the most commonly used mono-oximes. The sugar analogs were also less toxic than the non-sugar analogs; some also displayed higher efficacy. The mechanism underlying the improved features of the sugar oximes, and the structural requirements in relation to the sugar attachment to the oxime function, are discussed.
AB - A series of pyridinium aldoximes having a sugar conjugated to the pyridine ring has been prepared as potential antidotes against organophosphate poisoning. The sugar residue was attached either directly through C-1 or C-6 of the pyranose ring or through a C3 bridge between the glycosyl group and the nitrogen atom of the pyridine moiety. Attachment of a sugar group to the oxime derivative seems to increase the bioavailability of the antidote. The clearance rate of the sugar conjugates was significantly lower than that of their non-sugar analogs and thus they were retained longer in the blood circulation. The sugar derivatives were more potent in decreasing paraoxon-induced hypothermia (which is regulated within the central nervous system) than N-methyl-2-pyridiniumaldoxime methanesulfonate, one of the most commonly used mono-oximes. The sugar analogs were also less toxic than the non-sugar analogs; some also displayed higher efficacy. The mechanism underlying the improved features of the sugar oximes, and the structural requirements in relation to the sugar attachment to the oxime function, are discussed.
UR - http://www.scopus.com/inward/record.url?scp=0023050002&partnerID=8YFLogxK
U2 - 10.1016/S0008-6215(00)90353-7
DO - 10.1016/S0008-6215(00)90353-7
M3 - Article
AN - SCOPUS:0023050002
SN - 0008-6215
VL - 151
SP - 337
EP - 347
JO - Carbohydrate Research
JF - Carbohydrate Research
IS - C
ER -