【文章名】Hydrolytic Reactivity Trends among Potential Prodrugs of the O2-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity.
Hydrolytic Reactivity Trends among Potential Prodrugs of the O2-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity.
作者
Valdez, Carlos A.;Saavedra, Joseph E.;Showalter, Brett M.;Davies, Keith M.;Wilde, Thomas C.;Citro, Michael L.;Barchi, Joseph J., Jr.;Deschamps, Jeffrey R.;Parrish, Damon;El-Gayar, Stefan;Schleicher, Ulrike;Bogdan, Christian;Keefer, Larry K.;
[摘要]：Glycosylated diazeniumdiolates of structure R2NN(O)=NO-R' (R' = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R2NN(O)=NO- ion. Moreover, cleaving the acid-stable glycosides under alk. conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacol. to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R2NN(O)=NO-GlcNAc (where R2N = diethylamino or pyrrolidin-l-yl and GlcNAc = N-acetylglucosamin-l-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity.
