Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study
Articolo
Data di Pubblicazione:
2016
Citazione:
Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study / M. Colzani, D. Demaddis, G. Casali, M. Carini, G. Vistoli, G. Aldini. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 11:16(2016), pp. 1778-1789. ((Intervento presentato al 23. convegno National Meeting of the Medicinal-Chemistry-Division of the Italian-Chemical-Society (DCF-SCI) tenutosi a Salerno nel 2015.
Abstract:
Reactive carbonyl species (RCS) are endogenous or exogenous byproducts involved in the pathogenic mechanisms of different oxidative-based disorders. Detoxification of RCS by carbonyl quenchers is a promising therapeutic strategy. Among the most studied quenchers are aminoguanidine, hydralazine, pyridoxamine, and carnosine; their quenching activity towards four RCS (4-hydroxy-trans-2-nonenal, methylglyoxal, glyoxal, and malondialdehyde) was herein analyzed and compared. Their ability to prevent protein carbonylation was evaluated invitro by using an innovative method based on high-resolution mass spectrometry (HRMS). The reactivity of the compounds was RCS dependent: carnosine efficiently quenched 4-hydroxy-trans-2-nonenal, pyridoxamine was particularly active towards malondialdehyde, aminoguanidine was active towards methylglyoxal and glyoxal, and hydralazine efficiently quenched all RCS. Reaction products were generated invitro and were characterized by HRMS. Molecular modeling studies revealed that the reactivity was controlled by specific stereoelectronic parameters that could be used for the rational design of improved carbonyl quenchers.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
carbonyl quenching; liquid chromatography; mass spectrometry; molecular modeling; reactive carbonyl species
Elenco autori:
M. Colzani, D. Demaddis, G. Casali, M. Carini, G. Vistoli, G. Aldini
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