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

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 95; pp. 670 - 678
• Main Authors: Díaz-Urrutia, Christian A., Olea-Azar, Claudio A., Zapata, Gerald A., Lapier, Michel, Mura, Francisco, Aguilera-Venegas, Benjamín, Arán, Vicente J., López-Múñoz, Rodrigo A., Maya, Juan D.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.09.2012
• Subjects: Animals; Anions; Antiparasitic Agents - chemistry; Antiparasitic Agents - pharmacology; Antiparasitic Agents - toxicity; Biological Assay; Cell Death - drug effects; Cell Line; Computer Simulation; Cyclic voltammetry; Dimethyl Sulfoxide - chemistry; Electrochemical Techniques; Electrodes; Electron Spin Resonance Spectroscopy; ESR; Free radicals; Indazoles - chemistry; Indazoles - pharmacology; Indazoles - toxicity; Macrophages - drug effects; Mice; Models, Molecular; NADH, NADPH Oxidoreductases - chemistry; Spin Labels; Tetracyclic indazoles; Theoretical calculations; Trypanocidal activity; Trypanosoma cruzi - drug effects; Cyclic voltammetry; Free radicals; Trypanocidal activity; Theoretical calculations; Tetracyclic indazoles; ESR
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2012.04.076

Conformational mode adopted by compound 1 into the Trypanosoma cruzi trypanothione reductase active site. [Display omitted] ► 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. 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.