The pH of HNO donation is modulated by ring substituents in Piloty's acid derivatives: azanone donors at biological pH

Sirsalmath, Kiran T.; Suárez, Sebastián; Bikiel, Damián E.; Doctorovich, Fabio

doi:10.1016/j.jinorgbio.2012.10.008

Cited by 34 publications

(28 citation statements)

References 39 publications

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“…An analysis of 13 C NMR data and available crystal structures (Supporting Information), reveal that OHPY and NHPY compounds have distinctive 5 chemical shifts for their quaternary carbons (δ = 87.6 -90.2 ppm for OHPY vs. δ = 68.4 -76.5 ppm for NHPY). Thus, 13 C NMR spectroscopy conveniently allows the two isomers to be distinguished if crystal structures cannot be obtained.…”

Section: Scheme 2 Synthesis Of Ohpy Derivativesmentioning

confidence: 99%

“…Piloty's acid (PA) derivatives and acyloxy nitroso compounds (AcON) represent other types of HNO donors that have been developed with tunable half-lives. [12][13][14][15][16][17] Our group has recently reported two new series of HNO donors with half-lives that can be varied from minutes to hours under physiological conditions: (hydroxylamino)pyrazolone (HAPY) and (hydroxylamino)barbituric acid (HABA) derivatives. [18][19][20] In addition to these examples, the continued development of efficient HNO donors is important to expand the research tools available to understand the potential role of HNO in biological processes.…”

Section: Introductionmentioning

confidence: 99%

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Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

et al. 2016

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A new class of nitrosocarbonyl precursors, O-substituted hydroxamic acids with pyrazolone leaving groups (OHPY), is described.These compounds generate nitrosocarbonyl intermediates, which upon hydrolysis release nitroxyl (azanone, HNO) under physiologically relevant conditions. Pyrazolones have been used to confirm the generation of nitrosocarbonyls by competitive trapping to form isomeric N-substituted hydroxamic acids (NHPY) via an N-selective nitrosocarbonyl aldol reaction. The rate of nitrosocarbonyl release from OHPY donors is impacted by donor substituents, including the pyrazolone leaving group.

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Section: Scheme 2 Synthesis Of Ohpy Derivativesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

et al. 2016

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“…In contrast, the methoxy substituent is an electron releasing group and disfavours NO release in comparison with the Piloty’s acid parent compound. This trend is confirmed by N -hydroxy-4-fluorobenzenesulfonamide which, containing an electron withdrawing substituent, behaves similarly to the nitro derivative [ 45 ].…”

Section: Resultsmentioning

confidence: 94%

“…Therefore, EPR spectroscopy can be used to measure the amount and the rate of NO release from a series of NO-donors. It must be observed that under the experimental conditions used in this study PI derivatives can release also HNO as discussed in the Introduction [ 44 , 45 ].…”

Section: Methodsmentioning

confidence: 99%

“…Among all Piloty’s acid derivatives evaluated, N -Hydroxy-2-nitro-benzenesulfonamide and 2-bromo- N -hydroxybenzenesulfonamide have proven the most efficient HNO donors at pH = 7 releasing HNO in aqueous solution without co-production of NO [ 33 ]. A recent similar study conducted by Doctorovich et al, (2013) highlighted that, contrary to PI, N -hydroxybenzenesulfonamides with electron-attracting or withdrawing substituents in para-position on the aromatic ring behave preferentially as HNO donors operating at physiological pH and under strictly anaerobic condition [ 45 ]. On the contrary, a study published in the same year by Miyata et al, pointed out that Piloty’s acid derivatives having electron-withdrawing groups on the aromatic ring at the para-position released only a negligible amount of HNO by decomposition under physiological oxidative conditions [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Nitric Oxide Donors Derived from Piloty’s Acid and Study of Their Effects on Dopamine Secretion from PC12 Cells

et al. 2017

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This study investigated the mechanisms and kinetics of nitric oxide (NO) generation by derivatives of Piloty’s acid (NO-donors) under physiological conditions. In order to qualitatively and quantitatively measure NO release, electron paramagnetic resonance (EPR) was carried out with NO spin trapping. In addition, voltammetric techniques, including cyclic voltammetry and constant potential amperometry, were used to confirm NO release from Piloty’s acid and its derivatives. The resulting data showed that Piloty’s acid derivatives are able to release NO under physiological conditions. In particular, electron-withdrawing substituents favoured NO generation, while electron-donor groups reduced NO generation. In vitro microdialysis, performed on PC12 cell cultures, was used to evaluate the dynamical secretion of dopamine induced by the Piloty’s acid derivatives. Although all the studied molecules were able to induce DA secretion from PC12, only those with a slow release of NO have not determined an autoxidation of DA itself. These results confirm that the time-course of NO-donors decomposition and the amount of NO released play a key role in dopamine secretion and auto-oxidation. This information could drive the synthesis or the selection of compounds to use as potential drugs for the therapy of Parkinson’s disease (PD).

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How to Find an HNO Needle in a (Bio)‐Chemical Haystack

Doctorovich¹,

Bikiel²,

Pellegrino³

et al. 2014

Progress in Inorganic Chemistry

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The pH of HNO donation is modulated by ring substituents in Piloty's acid derivatives: azanone donors at biological pH

Cited by 34 publications

References 39 publications

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

Synthesis of Nitric Oxide Donors Derived from Piloty’s Acid and Study of Their Effects on Dopamine Secretion from PC12 Cells

How to Find an HNO Needle in a (Bio)‐Chemical Haystack

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