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Parasitology. 2014 Jul;141(8):1031-43. doi: 10.1017/S0031182014000201. Epub 2014 Mar 17.

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

Author information

  • 1Instituto de Química Médica, Centro de Química Orgánica M. Lora-Tamayo, CSIC,E-28006 Madrid,Spain.
  • 2Departamento de Parasitología, Facultad de Ciencias,Universidad de Granada,E-18071 Granada,Spain.
  • 3Departamento de Química Inorgánica,Instituto de Ciencia Molecular, Universidad de Valencia,E-46980 Paterna (Valencia),Spain.
  • 4Departamento de Química Orgánica, Facultad de Química,Universidad Complutense,E-28040 Madrid,Spain.
  • 5Departamento de Estadística. Facultad de Ciencias,Universidad de Granada,E-18071 Granada,Spain.

Abstract

The in vitro leishmanicidal activity and cytotoxicity of pyrazole-containing macrocyclic polyamines 1-4 was assayed on Leishmania infantum and Leishmania braziliensis species. Compounds 1-4 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 1-3 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.

PMID:
24636142
[PubMed - indexed for MEDLINE]
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