TY - JOUR
T1 - Comparison of the NO and HNO donating properties of diazeniumdiolates
T2 - Primary amine adducts release HNO in vivo
AU - Miranda, Katrina M.
AU - Katori, Tatsuo
AU - Torres De Holding, Claudia L.
AU - Thomas, Lynta
AU - Ridnour, Lisa A.
AU - McLendon, William J.
AU - Cologna, Stephanie M.
AU - Dutton, Andrew S.
AU - Champion, Hunter C.
AU - Mancardi, Daniele
AU - Tocchetti, Carlo G.
AU - Saavedra, Joseph E.
AU - Keefer, Larry K.
AU - Houk, K. N.
AU - Fukuto, Jon M.
AU - Kass, David A.
AU - Paolocci, Nazareno
AU - Wink, David A.
PY - 2005/12/29
Y1 - 2005/12/29
N2 - Diazeniumdiolates, more commonly referred to as NONOates, have been extremely useful in the investigation of the biological effects of nitric oxide (NO) and related nitrogen oxides. The NONOate Angeli's salt (Na 2N2O3) releases nitroxyl (HNO) under physiological conditions and exhibits unique cardiovascular features (i.e., positive inotropy/lusitropy) that may have relevance for pharmacological treatment of heart failure. In the search for new, organic-based compounds that release HNO, we examined isopropylamine NONOate (IPA/NO; Na[(CH 3)2-CHNH(N(O)NO]), which is an adduct of NO and a primary amine. The chemical and pharmacological properties of IPA/NO were compared to those of Angeli's salt and a NO-producing NONOate, DEA/NO (Na[Et 2NN(O)NO]), which is a secondary amine adduct. Under physiological conditions IPA/NO exhibited all the markers of HNO production (e.g., reductive nitrosylation, thiol reactivity, positive inotropy). These data suggest that primary amine NONOates may be useful as HNO donors in complement to the existing series of secondary amine NONOates, which are well-characterized NO donors.
AB - Diazeniumdiolates, more commonly referred to as NONOates, have been extremely useful in the investigation of the biological effects of nitric oxide (NO) and related nitrogen oxides. The NONOate Angeli's salt (Na 2N2O3) releases nitroxyl (HNO) under physiological conditions and exhibits unique cardiovascular features (i.e., positive inotropy/lusitropy) that may have relevance for pharmacological treatment of heart failure. In the search for new, organic-based compounds that release HNO, we examined isopropylamine NONOate (IPA/NO; Na[(CH 3)2-CHNH(N(O)NO]), which is an adduct of NO and a primary amine. The chemical and pharmacological properties of IPA/NO were compared to those of Angeli's salt and a NO-producing NONOate, DEA/NO (Na[Et 2NN(O)NO]), which is a secondary amine adduct. Under physiological conditions IPA/NO exhibited all the markers of HNO production (e.g., reductive nitrosylation, thiol reactivity, positive inotropy). These data suggest that primary amine NONOates may be useful as HNO donors in complement to the existing series of secondary amine NONOates, which are well-characterized NO donors.
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U2 - 10.1021/jm050151i
DO - 10.1021/jm050151i
M3 - Article
C2 - 16366603
AN - SCOPUS:23844527684
SN - 0022-2623
VL - 48
SP - 8220
EP - 8228
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 26
ER -