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Because redox properties are central to bioreductive drug activity and selectivity, six 2-methyl-5-nitroimidazole, substituted at the N1-ethyl side chain with I, Br, Cl, OAc, OMs and NH(3)(+) were synthesized and submitted to cyclic voltammetry and electrolyses, in order to define their electrodic reduction mechanism, in aprotic [dimethylsulphoxide (DMSO)+0.1 mol l(-1) tetrabuthylammonium perchlorate (TBAP)] and phosphate-buffered media, on glassy carbon electrode, in comparison with metronidazole. Three of these compounds, namely, the iodo, bromo and ammonium salt derivatives showed significant anti-Helicobacter pylori (strain resistant to metronidazole) activity. All the cyclic voltammograms (CV), in aprotic medium, are similar to the one for metronidazole, except for -I, -Br and -NH(3)(+) derivatives. The CV of the N1-ethylhalide (-I, -Br) 5-nitroimidazole showed more intense and irreversible first waves, even at faster sweep rates (nu2 V s(-1)). The absence of the first wave anodic counterpart, along with analysis of the dependence of E(p), I(p) and other parameters with nu, and results from electrolysis (consumption of two electrons) showed the process to be an ECE system, with halide release, after uptake of two electrons. This behaviour represents a case of dissociative electron transfer (ET). For the ammonium salt, self-protonation mechanism was evident. The facility of reduction represented by the first wave potential and concerning the substituents is NH(3)(+)BrIClOMsOHOAc. In aqueous phosphate-buffered medium, the electrochemical behaviour of all the compounds is similar to the one of metronidazole, represented by a unique and irreversible 4e(-)/4H(+) wave. The order of reduction ease is NH(3)(+)Br approximately OMsIOHOAc. Aprotic medium allows a better discrimination between the substituents. Concerning biological activity, despite the impossibility of establishing a correlation, it has been observed that the more electrophilic compounds showed better anti-H. pylori activity.

In search for new molluscicidal natural products, we have tested the activity of lapachol, its potassium salt and acetyl derivative against the snail Biomphalaria glabrata and its egg masses. The LD50 values for the salt (2.70 ppm and 1.43 ppm, respectively) and for lapachol (2.57 ppm and 0.190 ppm, respectively) are indicative of a strong activity. The methyl derivative is less active against adult snails (LD50 7.72 ppm) and egg masses (LD50 38.26 ppm) Lapachol derivatives were also assayed against infective trypomastigote blood forms of T. cruzi and the triacetoxy derivative of reduced lapachol showed relevant trypanocidal activity, killing 95.7% of the parasites at the concentration of 42 µg/mL. As lapachol is easily extracted and its derivatives synthesized without any difficulty, field tests can be conducted, with a perspective of application in large-scale molluscicidal programs.

In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3 H )-3-( N -3′-nitrophenylamino)naphtho[1,2- b ]furan-4,5-dione (QPhNO 2 ) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF 4 ) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO 2 . QPhNO 2 caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N -acetyl- l -cysteine partially abolished the observed effects related to the QPhNO 2 treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry.