Electrochemical parameters and techniques in drug development, with an emphasis on quinones and related compounds

Hillard, Elizabeth A.; Abreu, Fabiane Caxico de; Ferreira, Dalva E. C.; Jaouen, Gérard; Goulart, Marília Oliveira Fonseca; Amatore, Christian

doi:10.1039/b718116g

Cited by 194 publications

(173 citation statements)

References 149 publications

(189 reference statements)

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…[36][37][38][39][40][41][42] As already described, oxidative stress leading to DNA damage and alkylation of nuclear cellular nucleophiles are the two major mechanisms of quinone cytotoxicity. 9,12,16,43 Concerning the results in the present study, a typical electrochemical behavior (in aprotic medium) is observed for oncocalyxone A, represented by diffusional two quasi-reversible reduction systems, with a well-stabilized anion radical as evidenced by ESR analysis. Oncocalyxone A has shown significant DNA activity, represented by the decrease and shift of oxidation peaks of guanosine/guanine and adenosine/adenine.…”

Section: Discussionsupporting

confidence: 53%

“…3,4,[5][6][7][8] Oncocalyxone A also shows differential antitumor activity against the murine tumors Ehrlich carcinoma, sarcoma 180 and L1210 leukemia. 8 In general, two major mechanisms of quinone cytotoxicity have been proposed: stimulation of oxidative stress and alkylation of cellular nucleophiles, which encompass large range of biomolecules, 9 such as DNA and some enzymes, e.g., topoisomerase and protein tyrosine phosphatases, mainly those with thiol groups. 10 Oncocalyxone A, a para-benzoquinone with an extended conjugated dienone scaffold, may possibly function as a reactive Michael acceptor toward nucleophilic sites on proteins, for example, cysteinyl thiol groups, or on DNA.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oncocalyxone A: electrochemical, spectroscopic investigation and studies of its interaction with DNA, nucleobases and N-acetylcysteine

Costa¹,

Costa²,

Ferreira³

et al. 2012

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

A formação de espécies paramagnéticas a partir da oncocalixona A em meio aprótico foi confirmada pela realização de experimentos eletroquímicos in situ em conjunto com ressonância de spin eletrônico (E-ESR). A alta deslocalização do radical gerado no primeiro potencial de redução está claramente evidenciada pelo acoplamento hiperfino do H-9 com a maior constante de acoplamento, além dos acoplamentos nas posições H-3 (próximo à quinona) e H-7 (distante do núcleo quinônico). Em meio prótico, além dos experimentos de dependência com o pH, oncocalixona A mostrou-se DNA-reativa por meio de experimentos eletroquímicos com sensores de DNA. Sua reação com N-acetilcisteína, com caracterização estrutural dos produtos de adição, evidencia sua habilidade como aceptor de Michael. Ambos os aspectos são importantes em termos de atividades biológicas/farmacológicas e indicam os presentes modelos como ferramentas importantes na avaliação de compostos biologicamente ativos.The formation of paramagnetic species from oncocalyxone A in aprotic medium was confirmed by performing in situ electrochemical-electron spin resonance (E-ESR) experiments. The high delocalization of the radical generated at the first reduction potential is clearly evidenced by the hyperfine coupling of H-9 with the larger coupling constant, besides the couplings at the H-3 (close to quinone) and H-7 (far from the quinone nucleus) positions. In protic medium, together with pH dependence experiments, oncocalyxone A showed to be DNA-reactive through experiments with DNA sensors. Its reaction with N-acetylcysteine, with structural characterization of the addition products, proved its ability as Michael acceptor. Both aspects are important in terms of biological/ pharmacological activities and indicate the present models as important tools in the screening of biologically active compounds.Keywords: oncocalyxone A, spectroelectrochemical-electron spin resonance, DNA interaction, N-acetylcysteine, Michael acceptor IntroductionOncocalyxone A (rel-8α-hydroxy-5-hydroxymethyl-2 -m e t h o x y -8 a , β -m e t h y l -7 , 8 , 8 a , 9 -t e t r a h y d r o -1,4-anthracenedione) ( Figure 1a) is a natural parabenzoquinone isolated from Auxemma oncocalyx TAUB, popularly known as "pau branco", that belongs to the Boraginaceae family. 1,2 Oncocalyxone A exhibits a series of biological properties, 2 such as cytotoxic, analgesic and anti-inflammatory, it causes DNA damage and inhibition Costa et al. 1175 Vol. 23, No. 6, 2012 of platelet activation. 3,4,[5][6][7][8] Oncocalyxone A also shows differential antitumor activity against the murine tumors Ehrlich carcinoma, sarcoma 180 and L1210 leukemia. 8 In general, two major mechanisms of quinone cytotoxicity have been proposed: stimulation of oxidative stress and alkylation of cellular nucleophiles, which encompass large range of biomolecules, 9 such as DNA and some enzymes, e.g., topoisomerase and protein tyrosine phosphatases, mainly those with thiol groups. 10 Oncocalyxone A, a para-benzoquinone with an extended conjugated dienon...

show abstract

Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Oncocalyxone A: electrochemical, spectroscopic investigation and studies of its interaction with DNA, nucleobases and N-acetylcysteine

Costa¹,

Costa²,

Ferreira³

et al. 2012

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…6 A recent review shows how drug development can be aided by electrochemical investigations, with a focus on quinone compounds. 7 The studies of quinone electrochemistry also contributed to our understanding of proton-coupled electron transfer (PCET) reactions. A review on electrochemical approach to PCET mechanism devotes a great portion to quinones.…”

Section: Introductionmentioning

confidence: 99%

The Electrochemical Reaction Mechanism and Applications of Quinones

Kim¹,

Chung²

2014

Bulletin of the Korean Chemical Society

View full text Add to dashboard Cite

This tutorial review provides a general account of the electrochemical behavior of quinones and their various applications. Quinone electrochemistry has been investigated for a long time due to its complexity. A simple point of view is developed that considers the relative stability of the reduced quinone species and the values of the first and second reduction potentials. The 9-membered square scheme in buffered aqueous solutions is explained and semiquinone radical stability is discussed in this context. Quinone redox reaction has also been employed in various studies. Diverse examples are presented under three broad categories defined by the roles of quinone: molecular tool for physical chemistry, versatile electron mediator, and charge storage for energy conversion devices.

show abstract

“…This property can be related to their biological activity. [258][259][260] The potential of quinone compounds to participate in redox cycling is mainly dependent on the stability of the semiquinone radical relative to the quinone and the quinol forms. A simple and practical method for calculating thermodynamic parameters necessary to estimate semiquinone stability constants and redox potentials for quinone natural products has been reported by Cape et al 261 utilizing DFT-B3LYP method.…”

mentioning

confidence: 99%

Recent advances in 1,4-benzoquinone chemistry

Abraham¹,

Joshi²,

Pardasani³

et al. 2011

J. Braz. Chem. Soc.

169

View full text Add to dashboard Cite

As 1,4-benzoquinonas são encontradas em toda a natureza, podendo ser sintetizadas por diversas estratégias. Esta revisão apresenta os desenvolvimentos recentes das metodologias de síntese, das reações de ciclo adição, da química computacional e dos estudos de pulso radiolítico. Destaca ainda a sua significância química e biológica e de seus compostos derivados.1,4-Benzoquinones are ubiquitous in nature and can be synthesized by diverse strategies. Recent developments on their synthetic methodologies, cycloaddition reactions, computational chemistry and pulse radiolytic studies are reported in this review. Their chemical and biological significance as well as their derivates' are also covered.

show abstract

Electrochemical parameters and techniques in drug development, with an emphasis on quinones and related compounds

Cited by 194 publications

References 149 publications

Oncocalyxone A: electrochemical, spectroscopic investigation and studies of its interaction with DNA, nucleobases and N-acetylcysteine

Oncocalyxone A: electrochemical, spectroscopic investigation and studies of its interaction with DNA, nucleobases and N-acetylcysteine

The Electrochemical Reaction Mechanism and Applications of Quinones

Recent advances in 1,4-benzoquinone chemistry

Contact Info

Product

Resources

About