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Effect of the leaving group on the electrodic reduction mechanism of anti-Helicobacter pylori metronidazole derivatives, in aprotic and protic media

2004; Elsevier BV; Volume: 63; Issue: 1-2 Linguagem: Inglês

10.1016/j.bioelechem.2003.10.031

1878-562X

Janesmar C.M. Cavalcanti, Fabiane C. de Abreu, Natália Velasquez Oliveira, Maria Aline Barros Fidelis de Moura, J.G. Chaves, R.J. Alves, Massimo Bertinaria, Roberta Fruttero, Marília Oliveira Fonseca Goulart,

Microfluidic and Capillary Electrophoresis Applications

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 NH3+ 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 -NH3+ derivatives. The CV of the N1-ethylhalide (-I, -Br) 5-nitroimidazole showed more intense and irreversible first waves, even at faster sweep rates (ν Br>I>Cl>OMs>OH>OAc. 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 NH3+>Br∼OMs>I>OH>OAc. 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.