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

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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.

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Acknowledgments

The authors are grateful to the Spanish Ministries of Science and Innovation (MICINN ref SAF2009-10399) and Foreign Affairs and Cooperation (MAEC-AECID, ref A/030156/10) and to Universidad Complutense de Madrid Research Group “Terapia Antiparasitaria” (UCM-BSCH, ref 911120) for the financial support. Research by Cristina Fonseca-Berzal has been also supported by a PICATA predoctoral fellowship of the Moncloa Campus of International Excellence (UCM-UPM & CSIC). The authors thank to LAFEPE, Pernambuco, Brazil, for kindly providing benznidazole raw product.

Ethical standards

The authors declare that all the experiments comply with the current laws of Spain.

Conflict of interest

The authors declare that they have no conflict of interest in the present study.

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Authors and Affiliations

  1. Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid (CEI Campus Moncloa, UCM-UPM & CSIC), Pza. Ramón y Cajal s/n, 28040, Madrid, Spain

    Cristina Fonseca-Berzal, José Antonio Escario & Alicia Gómez-Barrio

  2. Instituto de Química Médica (IQM), CSIC (CEI Campus Moncloa, UCM-UPM & CSIC), c/ Juan de la Cierva 3, 28006, Madrid, Spain

    Vicente J. Arán

Authors
  1. Cristina Fonseca-Berzal
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  2. José Antonio Escario
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  3. Vicente J. Arán
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  4. Alicia Gómez-Barrio
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Correspondence to Cristina Fonseca-Berzal.

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Fonseca-Berzal, C., Escario, J.A., Arán, V.J. et al. Further insights into biological evaluation of new anti-Trypanosoma cruzi 5-nitroindazoles. Parasitol Res 113, 1049–1056 (2014). https://doi.org/10.1007/s00436-013-3740-5

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  • DOI: https://doi.org/10.1007/s00436-013-3740-5

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