Biological and chemical study of fused tri- and tetracyclic indazoles and analogues with important antiparasitic activity

A series of fused tri- and tetracyclic indazoles and analogues compounds (NID) with potential antiparasitic effects were studied using voltamperometric and spectroscopic techniques. Nitroanion radicals generated by cyclic voltammetry were characterized by electron spin resonance spectroscopy (ESR) and their spectral lines were explained and analyzed using simulated spectra. In addition, we examined the interaction between radical species generated from nitroindazole derivatives and glutathione (GSH). Biological assays such as activity against Trypanosoma cruzi and cytotoxicity against macrophages were carried out. Finally, spin trapping and molecular modeling studies were also done in order to elucidate the potentials action mechanisms involved in the trypanocidal activity.

Conformational mode adopted by compound 1 into the Trypanosoma cruzi trypanothione reductase active site.Figure optionsDownload as PowerPoint slideHighlight
► In this study we characterized the electrochemistry mechanism of tetracylic indazoles. The radicals species generated were register using electron spin resonance spectroscopy. This family was also evaluated as potential tripanocide.