Reaction of sydnones with ozone as a method of deamination: on the mechanism of inhibition of monoamine oxidase by sydnones

White, Emil H.; Egger, Notker

doi:10.1021/ja00324a067

Cited by 18 publications

(4 citation statements)

References 2 publications

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“…15). 135 The heme adduct isolated from rats treated with the sydnone has been identified as N-vinylprotoporphyrin IX. Activation of the sydnone by hydroxylation of the electron-rich zwitterionic carbon, followed by ring opening and elimination of the carboxylic fragment to give the diazo species (Fig.…”

Section: N-n Functionsmentioning

confidence: 99%

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Inhibition of Cytochrome P-450 Enzymes

Montellano

Reich

1986

Cytochrome P-450

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Section: N-n Functionsmentioning

confidence: 99%

“…The chemical oxidation of sydnones has been shown to proceed by this mechanism. 135 The diazoalkane, in turn, reacts with the heme, possibly via an initial carbene complex, to give a nitrogen-iron bridged species. The formation of such bridged nitrogen-iron species has been documented in model porphyrin systems.…”

Section: N-n Functionsmentioning

confidence: 99%

Inhibition of Cytochrome P-450 Enzymes

Montellano

Reich

1986

Cytochrome P-450

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“…The catalytic role of the enzyme in its own inactivation, the structure of the resulting heme adduct, the observation that pyruvic acid is concomitantly released, and the results of earlier model studies on the oxidation of sydnones (White & Egger, 1984) led us to formulate the mechanism in Scheme I for destruction of cytochrome P-450 by TTMS. Thus, cytochrome P-450 catalyzed hydroxylation of the sydnone ring triggers elimination of pyruvic acid and formation of the corresponding alkyldiazonium cation.…”

mentioning

confidence: 99%

Cytochrome P-450 inactivation by 3-alkylsydnones. Mechanistic implications of n-alkyl and n-alkenyl heme adduct formation

Grab¹,

Swanson²,

Montellano³

1988

Biochemistry

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Incubation of 3-(2-phenylethyl)-4-methylsydnone (PMS) with liver microsomes from phenobarbital-pretreated rats or with reconstituted cytochrome P-450b results in loss of the enzyme chromophore. Chromophore loss is NADPH-dependent even though the sydnone decomposes by an oxygen- but not enzyme-dependent process to give pyruvic acid and, presumably, the (2-phenylethyl)diazonium cation. N-(2-Phenylethyl)protoporphyrin IX and N-(2-phenylethenyl)protoporphyrin IX have been isolated from the livers of rats treated with PMS. Both deuteriums are retained in the N-(2-phenylethyl) adduct derived from 3-(2-phenyl[1,1-2H]ethyl)-4-methylsydnone, but one deuterium is lost in the N-(2-phenylethenyl) adduct. The N-(2-phenylethyl) to N-(2-phenylethenyl) adduct ratio is increased by deuterium substitution. No spectroscopically detectable intermediates precede chromophore loss in incubations of reconstituted cytochrome P-450b with PMS. Electron paramagnetic resonance (EPR)-spin trapping studies show that carbon radicals are formed in incubations of the sydnones with liver microsomes but by a process that is independent of chromophore destruction. It is proposed that the 2-phenylethyl radical formed by electron transfer to the sydnone-derived (2-phenylethyl)diazonium cation adds to the prosthetic heme group to give the N-(2-phenylethyl) adduct. This alkylation reaction is similar to that observed with (2-phenylethyl)hydrazine. Autoxidation of the Fe-CH(CH2Ph)-N bridged species expected from insertion of 2-phenyldiazoethane into one of the heme Fe-N bonds is proposed to explain the unprecedented introduction of a double bond into the N-(2-phenylethenyl) adduct.

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“…Besides these unique physical and chemical properties, they also possess various bioactivities, such as antifungal [ 4 ], anti-inflammatory [ 5 , 6 , 7 ], and analgesic activities [ 8 , 9 , 10 , 11 ]. They are inhibitors of cyclic AMP phosphodiesterase and antagonists of adenosine receptors [ 12 , 13 ], and show antibacterial [ 14 , 15 , 16 ], anti-tumor [ 17 ], and insecticidal [ 18 , 19 , 20 , 21 , 22 ] activities. Encouraged by these characteristics of mesoionic compounds, many researchers have studied the potential applications of mesoionics [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Insecticidal Activity of Mesoionic Pyrido[1,2-α]pyrimidinone Derivatives Containing a Neonicotinoid Moiety

Pan

Liu

et al. 2018

Molecules

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Mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety were designed, synthesized, and evaluated for their insecticidal activity. Some of the title compounds showed remarkable insecticidal properties against Aphis craccivora. Compound I13 exhibited satisfactory insecticidal activity against A. craccivora. Meanwhile, label-free proteomics analysis of compound I13 treatment identified a total of 821 proteins. Of these, 35 proteins were up-regulated, whereas 108 proteins were down-regulated. Differential expressions of these proteins reflected a change in cellular structure and metabolism.

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Reaction of sydnones with ozone as a method of deamination: on the mechanism of inhibition of monoamine oxidase by sydnones

Cited by 18 publications

References 2 publications

Inhibition of Cytochrome P-450 Enzymes

Inhibition of Cytochrome P-450 Enzymes

Cytochrome P-450 inactivation by 3-alkylsydnones. Mechanistic implications of n-alkyl and n-alkenyl heme adduct formation

Synthesis and Insecticidal Activity of Mesoionic Pyrido[1,2-α]pyrimidinone Derivatives Containing a Neonicotinoid Moiety

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