Fabiane Caxico de Abreu

Trypanocidal activity and redox potential of heterocyclic- and 2-hydroxy-naphthoquinones

Abstract With the aim of understanding the influence of redox potentials on the trypanocidal activity, a series of quinones were tested in vitro with trypomastigotes of Trypanosoma cruzi and their first cathodic potentials (Epcl) measured by cyclic voltammetry. All quinones with Epcl > −0.72V were active, while most of those with Epcl

Synthesis and cytotoxic activity of new acridine-thiazolidine derivatives

Although their exact role in controlling tumour growth and apoptosis in humans remains undefined, acridine and thiazolidine compounds have been shown to act as tumour suppressors in most cancers. Based on this finding, a series of novel hybrid 5-acridin-9-ylmethylene-3-benzyl-thiazolidine-2,4-diones were synthesised via N-alkylation and Michael reaction. The cell viability was analysed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and DNA interaction assays were performed using electrochemical techniques.

Electroanalytical determination of carbendazim by square wave adsorptive stripping voltammetry with a multiwalled carbon nanotubes modified electrode

A preconcentrating/voltammetric multiwalled carbon nanotube modified glassy carbon electrode (MWCNT–GCE) has been developed for stripping analysis of carbendazim (Methyl Benzimidazol-2-yl Carbamate—MBC), based on dispersing MWCNT in water. The effect of experimental variables, such as the dispersion and loading of MWCNT, was assessed. A quasi-reversible behavior for MBC in acetic acid/acetate buffer 0.1 mol L−1 (pH 4.7) was verified and its high effective pre-concentration was attributed to the high adsorption capability and enormous surface area of the MWCNT. No evidence of carry-over effect, combined with the easiness of electrode preparation, led to the development of a highly sensitive and reliable method with an experimental work range from 0.256 to 3.11 µmol L−1 with a detection limit of 10.5 ppb for a short (60 s) accumulation period. Measurement of MBC in a river water sample was demonstrated. The accuracy of the method for real sample analysis was assessed by estimating the apparent recovery (93 ± 2.9% and 86 ± 4.1% for 4.3 × 10−7 mol L−1) for a MBC spiked river water sample.

Electrochemical Properties of Biologically Active Heterocyclic Naphthoquinones

Uma serie de naftoquinonas heterociclicas naturais e sinteticas, algumas delas com atividades anti-plasmodio e tripanosomicida comprovadas, foi estudada atraves de voltametria ciclica em meio aprotico (DMF/TBAP). Os voltamogramas apresentaram dois pares de ondas, relativos a processos reversiveis ou quase-reversiveis de transferencia monoeletronicos, formando, no ramo catodico, o ânion-radical semiquinonico (Q·) e, em seguida, o diânion (Q2-). Orto-naftoquinonas sofreram reducao mais facilmente do que para-naftoquinonas similares. Para-naftoquinonas fundidas a um heterociclo aromatico mostraram-se mais facilmente redutiveis do que orto-naftoquinonas ostentando heterociclos nao aromaticos. Efeitos dos substituintes correlacionam-se bem com os valores de potencial de reducao de primeira onda (Epc1) e de potencial de meia onda (E1/2). Eletrolises realizadas em presenca de anidrido acetico forneceram hidroquinonas acetiladas em alto rendimento. Comparacao dos dados eletroquimicos com atividades anti-plasmodio evidenciou ausencia de correlacao, diferentemente do registrado em relacao as atividades tripanosomicidas.

Nature of Electrogenerated Intermediates in Nitro-Substituted Nor-β- lapachones: The Structure of Radical Species during Successive Electron Transfer in Multiredox Centers

Electrochemical, spectroelectrochemical, and theoretical studies of the reduction reactions in nor-β-lapachone derivatives including a nitro redox center showed that reduction of the compounds involves the formation of several radical intermediates, including a biradical dianion resultant from the separate reduction of the quinone and nitro groups in the molecules. Theoretical descriptions of the corresponding Fukui functions f(αα)⁺ and f(ββ)⁺(r) and LUMO densities considering finite differences and frozen core approximations for describing the changes in electron and spin densities of the system allowed us to confirm these results. A description of the potential relationship with the obtained results and biological activity selectivity indexes suggests that both the formation of stable biradical dianion species and the stability of the semiquinone intermediates during further reduction are determining factors in the description of their biological activity.

Correlation between electrochemical and theoretical studies on the leishmanicidal activity of twelve Morita-Baylis-Hillman adducts

Enzymatic bioreduction of nitro groups plays an important role on the activity of biologically active nitroaromatic compounds. Electrochemical methods are useful tools to simulate in vivo metabolic processes. This work presents electrochemical studies in aprotic media (N, N-dimethylformamide (DMF) plus tetrabutylammonium perchlorate (TBAP) 0.1 mol L-1) using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV) of twelve Morita-Baylis-Hillman adducts (MBHA) with significant leishmanicidal activity. To facilitate the analysis, the molecules were grouped in four classes according to the side chain. CV studies show three up to four reduction waves, in which the first two waves are related to nitro group reduction. The other waves (presenting more negative potential) refer to the reduction of the α,β-unsaturated carbonyl or to the nitrile activated olefin side-chain. Ortho adducts present facilitated reduction in comparison to the other isomers (meta and para) possibly due to hydrogen bond formation between the benzylic-OH and the nitro group, which stabilizes the reduction product (anion radical nitro) more efficiently than the original compound. Ortho derivatives also present higher leishmanicidal activity upon comparison to the other derivatives of each class. Conformational studies using HF/6-31+G(d)/PCM as a calculation level highlight this effect. Molecular hardness (N) and atomic charges (QN) values corroborate the obtained experimental data.

Determination of the pKa values of some biologically active and inactive hydroxyquinones

The apparent dissociation constants (pKa) of four 2-hydroxynaphthoquinones, differently substituted at C-3, were determined in water:ethanol (1:1, v/v) solutions by pH-metric and hybrid pH-metric/UV titration methods. Isolapachol (pKa 6). Two pKa values were determined for each of the methylamino-derivatives investigated, the first relating to the enol function and the second to the ammonium salt. It was determined that under physiological pH, these derivatives would be to a large extension, zwitterionic. The possible effects of the measured parameters on the biological activities of the studied compounds are discussed.

Evaluation of a Portable Microchip Electrophoresis Fluorescence Detection System for the Analysis of Amino Acid Neurotransmitters in Brain Dialysis Samples.

A portable fluorescence detection system for use with microchip electrophoresis was developed and compared to a benchtop system. Using this system, six neuroactive amines commonly found in brain dialysate (arginine, citrulline, taurine, histamine, glutamate, and aspartate) were derivatized offline with naphthalene-2,3-dicarboxaldehyde/cyanide, separated electrophoretically, and detected by fluorescence. The limits of detection for the analytes of interest were 50 - 250 nM for the benchtop system and 250 nM - 1.3 μM for the portable system, both of which were adequate for most analyte detection in brain microdialysis samples. The portable system was then demonstrated for the detection of the same six amines in a rat brain microdialysis sample.

Molecular mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene on HL-60 leukemia cells.

The aim of this work was to investigate the mechanism of action of 2‐ferrocenyl‐1,1‐diphenylbut‐1‐ene (1) on HL‐60 human leukemia cells. While inactive against noncancerous cells, 1 provoked a concentration‐dependent decrease in viable tumor cells, primarily via apoptosis, as evidenced by analysis of cell morphology, activation of caspases 3 and 7, increased DNA fragmentation, and externalization of phosphatidylserine. Necrosis was observed only at the highest tested concentration (4 μM). Compound 1 interfered with the cell cycle, causing an accumulation of cells in the G1/G0 phase. Interaction of 1 with dsDNA and ssDNA was observed by differential pulse voltammetry and confirmed by hyperchromicity in the UV/Vis spectra of dsDNA, with an interaction constant of 2×104 M−1. Both the organic analogue 1,1,2‐triphenylbut‐1‐ene (2) and ferrocene were inactive against cancer and noncancer cell lines and did not react with DNA. These results reinforce the idea that the hybrid strategy of conjugating ferrocene to the structure of tamoxifen derivatives is advantageous in finding new substances with antineoplastic activity.

Electrochemical behavior of metribuzin on a glassy carbon electrode in an aqueous medium including quantitative studies by anodic stripping voltammetry

The electrochemical behavior of the herbicide metribuzin was studied in an aqueous solution on glassy carbon, carbon paste/Nujol oil and carbon paste/castor oil using cyclic voltammetry, square-wave voltammetry, differential pulse voltammetry, controlled-potential coulometry and electrolysis, for quantification and decontamination purposes. The main electrolytic products obtained from the reduction of metribuzin, after consumption of 8.26 mol electron mol-1, were deaminometribuzin and diketometribuzin. The anodic wave observed after electroreduction is associated with the oxidation of the methylthiolate generated in the electrolytic process. This wave was used to quantitatively determine metribuzin in a commercial sample by anodic stripping voltammetry. The electro-Fenton method was employed to promote decontamination by eliminating the herbicide, resulting in 80% of mineralization of the metribuzin.