Details

Autor(en) / Beteiligte

• Rodríguez, Jorge
• Arán, Vicente J.
• Boiani, Lucía
• Olea-Azar, Claudio
• Lavaggi, María Laura
• González, Mercedes
• Cerecetto, Hugo
• Maya, Juan Diego
• Carrasco-Pozo, Catalina
• Cosoy, Hernán Speisky

Titel

New potent 5-nitroindazole derivatives as inhibitors of Trypanosoma cruzi growth: Synthesis, biological evaluation, and mechanism of action studies

Ist Teil von

• Bioorganic & medicinal chemistry, 2009-12, Vol.17 (24), p.8186-8196

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• New 5-nitroindazole derivatives were developed and studied as antiproliferative Trypanosoma cruzi agents. New 5-nitroindazole derivatives were developed and their antichagasic properties studied. Eight compounds ( 14–18, 20, 26 and 28) displayed remarkable in vitro activities against Trypanosoma cruzi ( T. cruzi). Its unspecific cytotoxicity against macrophages was evaluated being not toxic at a concentration at least twice that of T. cruzi IC 50, for some derivatives. The electrochemical studies, parasite respiration studies and ESR experiment showed that 5-nitroindazole derivatives not be able to yield a redox cycling with molecular oxygen such as occurs with nifurtimox (Nfx). The study on the mechanism of action proves to be related to the production of reduced species of the nitro moiety similar to that observed with benznidazole.