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

Abstract

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...

Molecular Mechanism of Action of 2‐Ferrocenyl‐1,1‐diphenylbut‐1‐ene on HL‐60 Leukemia Cells

“…Electrochemistry of ssDNA in solution : To produce ssDNA by acid–base treatment, dsDNA (1 mg) was dissolved in 1 M HCl (100 μL) by heating at 100 °C in a sealed glass tube immersed in a boiling water bath for 1 h, followed by neutralization with 1 M NaOH 29. 30 A freshly prepared solution, consisting of 4 mL ssDNA and 950 μL of ethanol,28–30 was added to the electrochemical cell. Single‐scan DPV experiments were conducted between 0 and +1.4 V versus Ag|AgCl, KCl (0.1 M ), ( ν =10 mV s −1 , pulse amplitude=50 mV and pulse width=70 ms).…”

Oncocalyxone A Functions As an Anti-Glycation Agent In Vitro

“…Onco A exhibited various activities in vivo , including cytotoxic, analgesic and antioxidant functions, and inhibitory effects on inflammation, edema, platelet aggregation and tumorigenicity [ 10 , 13 , 14 , 15 ]. Additionally Onco A is known to inhibit cell growth by damaging DNA [ 15 , 16 ]. Strikingly, [ 17 ] reported that Onco A isolated from leaves of Prenanthes sarmentosus exerted anti-diabetic effects in rats with alloxan-induced diabetes.…”