Electrochemical methods are powerful in the characterization and design of redox-modulating agents. We, herein, report the electrochemical investigation, in aprotic medium, of eleven synthetic 3-thio-substituted-nor-beta-lapachones, along with the determination of cytotoxic activity and correspondent selectivity index, against several cancer cell lines and one normal cell. Four of the quinones are novel compounds. The redox behavior is representative of two independent systems: the easy reduction of the quinone moiety and, at far more negative potential, the reductive cleavage of the C-S-C bonding; and the anodic part controlled by the oxidation of the sulfur moiety. The compounds have shown relevant cytotoxic activity, with emphasis on 3-phenyl-thio-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione (compound 2), which mechanism of molecular action was shown to be related to reactive oxygen species (ROS) release. Despite the absence of a linear correlation, there is a trend: the majority of the thionaphthoquinones, with values of first wave reduction potential, less negative than -0.65 V, were active. The less electrophilic compound (3-(cyclohexylthio)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione, cyclohexyl derivative) is also the less cytotoxic toward cancer cells. Agents containing chalcogens and quinones can be used to attack entities with a disturbed redox balance.

O processo de biorredução enzimática do grupo nitro é de grande importância para a ação molecular de nitrocompostos aromáticos biologicamente ativos. Os métodos eletroquímicos são considerados ferramentas úteis para a simulação de processos metabólicos in vivo. No presente trabalho, realizaram-se estudos eletroquímicos em meio aprótico (N, N-dimetilformamida (DMF) mais perclorato de tetrabutilamônio (TBAP) 0,1 mol L-1) utilizando-se as técnicas de voltametria cíclica (CV), de pulso diferencial (DPV) e de onda quadrada (SWV) de 12 adutos de Morita-Baylis-Hillman (MBHA) com atividade leishmanicida significativa. Para facilitar a análise, os adutos foram agrupados em quatro classes de acordo com a cadeia lateral. Os estudos de CV evidenciam duas ondas referentes à redução do grupo nitro e uma ou duas outras ondas (em potencial mais negativo) relativas à redução da função carbonila α,β-insaturada ou da olefina ativada por grupos nitrila. Adutos orto-substituídos apresentam maior facilidade de redução quando comparados aos demais isômeros (meta e para) em função, provavelmente, da ligação de hidrogênio entre o grupo nitro e a hidroxila benzílica, o que estabiliza mais o produto eletrogerado do que o composto de partida. Derivados orto também mostram uma maior atividade leishmanicida em comparação com seus isômeros em cada série. Estudos conformacionais usando HF/6-31+G(d)/PCM como nível de cálculo evidenciaram este efeito. Valores calculados de dureza molecular (N) e de cargas atômicas (Q N) explicam corretamente os dados experimentais obtidos.

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 (Q N) values corroborate the obtained experimental data.