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In vitro leishmanicidal activity of pyrazole-containing polyamine macrocycles which inhibit the Fe-SOD enzyme of Leishmania infantum and Leishmania braziliensis species

  • P. NAVARRO (a1), M. SÁNCHEZ-MORENO (a2), C. MARÍN (a2), E. GARCÍA-ESPAÑA (a3), I. RAMÍREZ-MACÍAS (a2), F. OLMO (a2), M. J. ROSALES (a2), F. GÓMEZ-CONTRERAS (a4), M. J. R. YUNTA (a4) and R. GUTIERREZ-SÁNCHEZ (a5)...

Summary

The in vitro leishmanicidal activity and cytotoxicity of pyrazole-containing macrocyclic polyamines 14 was assayed on Leishmania infantum and Leishmania braziliensis species. Compounds 14 were more active and less toxic than glucantime and both infection rates and ultrastructural alterations confirmed that 1 and 2 were highly leishmanicidal and induced extensive parasite cell damage. Modifications in the excretion products of parasites treated with 13 were also consistent with substantial cytoplasm alterations. Compound 2 was highlighted as a potent inhibitor of Fe-SOD in both species, whereas its effect on human CuZn-SOD was poor. Molecular modelling suggested that 2 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the enzyme`s antioxidant features.

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Corresponding author

* Corresponding author: Instituto de Química Médica, Centro de Química Orgánica M. Lora-Tamayo, CSIC, E-28006 Madrid, Spain. E-mail: fercon@ucm.es and iqmnt38@iqm.csic.es

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Keywords

In vitro leishmanicidal activity of pyrazole-containing polyamine macrocycles which inhibit the Fe-SOD enzyme of Leishmania infantum and Leishmania braziliensis species

  • P. NAVARRO (a1), M. SÁNCHEZ-MORENO (a2), C. MARÍN (a2), E. GARCÍA-ESPAÑA (a3), I. RAMÍREZ-MACÍAS (a2), F. OLMO (a2), M. J. ROSALES (a2), F. GÓMEZ-CONTRERAS (a4), M. J. R. YUNTA (a4) and R. GUTIERREZ-SÁNCHEZ (a5)...

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