One-electron reduction of daunomycin, daunomycinone, and 7-deoxydaunomycinone by the xanthine/xanthine oxidase system: detection of semiquinone free radicals by electron spin resonance

Schreiber, Jörg; Mottley, Carolyn; Sinha, Birandra K.; Kalyanaraman, Balaraman; Mason, Ronald P.

doi:10.1021/ja00236a009

Cited by 72 publications

(34 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated previously that the orthosemiquinone stabilization by Mg +2 is due to a shift in the semiquinone disproportionation equilibrium towards the semiquinone [31]. Some broad component is observed in these EPR spectra indicating possible aggregation of a fraction of these semiquinones with neutral quinone or hydroquinone in analogy to what is observed for anthracycline semiquinones [22]. These observations are analogous to those previously made where complexation to multivalent cations is needed to stabilize orthosemiquinones while parase-miquinones are not [31].…”

Section: Gsh Reduction Of Quinonessupporting

confidence: 79%

“…The latter should correspond to aggregates of the semiquinone to neutral parent quinones and/or the corresponding hydroquinone. Similar aggregates in aqueous solutions have been observed for other semiquinones such as anthracyclines [22]. A single broad line with peak-to-peak width of 2 Gauss with identical gvalue to that of the aqueous phase species was used as the starting broad spectral component in the optimization process.…”

Section: Quinone Reduction By Gshmentioning

confidence: 59%

See 1 more Smart Citation

Thiols oxidation and covalent binding of BSA by cyclolignanic quinones are enhanced by the magnesium cation

Alegrı́a

Sanchez-Cruz

Kumar

et al. 2008

Free Radical Research

View full text Add to dashboard Cite

A novel cyclolignanic quinone, 7-acetyl-3′,4′-didemethoxy-3′,4′-dioxopodophyllotoxin (CLQ), inhibits topoisomerase II (TOPO II) activity. The extent of this inhibition was greater than that produced by the etoposide quinone (EQ) or etoposide. Glutathione (GSH) reduces EQ and CLQ to their corresponding semiquinones under anaerobic conditions. The latter were detected by EPR spectroscopy in the presence of MgCl 2 but not in its absence. Semiquinone EPR spectra change with quinone/GSH mol ratio, suggesting covalent binding of GSH to the quinones. Quinone-GSH covalent adducts were isolated and identified by ESI-MS. These orthoquinones also react with nucleophilic groups from BSA to bind covalently under anaerobic conditions. BSA thiol consumption and covalent binding by these quinones are enhanced by MgCl 2 . Complex formation between the parent quinones and Mg +2 was also observed. Density functional calculations predict the observed blueshifts in the absorption spectra peaks and large decreases in the partial negative charge of electrophilic carbons at the quinone ring when the quinones are complexed to Mg +2 . These observations suggest a possible role of Mg +2 chelation by these quinones in increasing TOPO II thiol and/or amino/imino reactivity with these orthoquinones.

show abstract

Section: Gsh Reduction Of Quinonessupporting

confidence: 79%

Section: Quinone Reduction By Gshmentioning

confidence: 59%

Thiols oxidation and covalent binding of BSA by cyclolignanic quinones are enhanced by the magnesium cation

Alegrı́a

Sanchez-Cruz

Kumar

et al. 2008

Free Radical Research

View full text Add to dashboard Cite

show abstract

“…Among the interactions that play a central role in this issue, the formation of inter-or intramolecular hydrogen bonds in these molecules plays a key role [232,233,234]. A recent electrochemical study about quinones possessing intramolecular hydrogen bonds (IHBs) shows that this interaction stabilizes the anion radical structure, leading to a shift in reduction potentials toward less negative values when compared with quinones without IHBs [235].…”

Section: Intramolecular Hydrogen Bondsmentioning

confidence: 99%

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

Yunta¹

2017

AJMO

View full text Add to dashboard Cite

The effect of weak intermolecular interactions on the binding affinity between ligand-protein complexes plays an important role in stabilizing a ligand at the interface of a protein structure. In this review article, we will explore the different ways of taking into account these interactions, mainly intramolecular hydrogen bonds, in docking calculations. Their possible limitations and their suitable application domains are highlighted. Inspection of the outliers of this study probed very stimulating, as it provides opportunities and inspiration to medicinal chemists, being a reminder of the impact that minimal chemical modifications can have on biological activities.

show abstract

“…The presence of semiquinone metabolites of anthracyclines has been demonstrated with ESR in anaerobic incubations containing microsomes, purified NADPH-cytochrome P450 reductase, and even in incubations of tumor cells (3). Analysis of the high-resolution ESR spectrum of the enzymatically generated daunorubicin semiquinone was reported recently (18).…”

Section: Quinonesmentioning

confidence: 99%

Redox cycling of radical anion metabolites of toxic chemicals and drugs and the Marcus theory of electron transfer.

Mason

1990

Environ Health Perspect

View full text Add to dashboard Cite

A wide variety of aromatic compounds are enzymatically reduced to form anion free radicals that generally contain one more electron than their parent compounds. In general, the electron donor is any of a wide variety of flavoenzymes. Once formed, these anion free radicals reduce molecular oxygen to superoxide and regenerate the parent compound unchanged. The net reaction is the oxidation of the flavoenzyme's coenzymes and the reduction of molecular oxygen. This catalytic behavior has been described as futile metabolism or redox cycling. Electron transfer theory is being applied to these reactions and, in some cases, has successfully correlated V., and Km with the reduction potentials of the aromatic compounds.

show abstract

One-electron reduction of daunomycin, daunomycinone, and 7-deoxydaunomycinone by the xanthine/xanthine oxidase system: detection of semiquinone free radicals by electron spin resonance

Cited by 72 publications

References 0 publications

Thiols oxidation and covalent binding of BSA by cyclolignanic quinones are enhanced by the magnesium cation

Thiols oxidation and covalent binding of BSA by cyclolignanic quinones are enhanced by the magnesium cation

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

Redox cycling of radical anion metabolites of toxic chemicals and drugs and the Marcus theory of electron transfer.

Contact Info

Product

Resources

About