Further insights into biological evaluation of new anti-Trypanosoma cruzi 5-nitroindazoles.

Abstract

Twelve molecules from a series of 35 new 5-nitroindazole derivatives, selected from a successful primary screening on Trypanosoma cruzi epimastigotes, have been evaluated against intracellular amastigotes according to the previous results of their trypanocidal activity and unspecific cytotoxicity. 2-Benzyl-1-propyl (22), 2-benzyl-1-isopropyl (23), and 2-benzyl-1-butyl (24) 5-nitroindazolin-3-ones have inhibited the growth of amastigotes similarly to the reference drugs benznidazole and nifurtimox, inducing complete growth inhibition at concentrations lower than 8 μM (IC₅₀ < 5 μM) and accomplishing great selectivity indexes on the intracellular form of the parasite (SI > 30). Further in vivo assays were developed only for two of the most active molecules (22 and 24), reaching significant reductions in parasitemia levels (52 % and 77%, respectively) after their oral administration to infected mice. In addition, none of the mice in experimental and benznidazole groups died, unlike in the control group which is only treated with the vehicle. The trypanocidal properties found in some of the 5-nitroindazole derivatives assayed in the present work represent an interesting contribution to the urgent need for searching new antichagasic drugs.

• Authors: Cristina Fonseca-Berzal, José Antonio Escario, Vicente J Arán, Alicia Gómez-Barrio
• Journal: Parasitology research (Parasitol Res) Vol. 113 Issue 3 Pg. 1049-56 (Mar 2014) ISSN: 1432-1955 [Electronic] Germany
• PMID: 24435615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indazoles
• Trypanocidal Agents
• 5-nitroindazole

Topics

• Animals
• Cell Line
• Indazoles (chemistry, pharmacology)
• Mice
• Trypanocidal Agents (pharmacology)
• Trypanosoma cruzi (drug effects)