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

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.
AuthorsP Navarro, M Sánchez-Moreno, C Marín, E García-España, I Ramírez-Macías, F Olmo, M J Rosales, F Gómez-Contreras, M J R Yunta, R Gutierrez-Sánchez
JournalParasitology (Parasitology) Vol. 141 Issue 8 Pg. 1031-43 (Jul 2014) ISSN: 1469-8161 [Electronic] England
PMID24636142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiprotozoal Agents
  • Macrocyclic Compounds
  • Polyamines
  • Protozoan Proteins
  • Pyrazoles
  • pyrazole
  • Superoxide Dismutase
  • Animals
  • Antiprotozoal Agents (chemistry, pharmacology)
  • Cell Line
  • Cell Survival (drug effects)
  • Erythrocytes (drug effects)
  • Female
  • Humans
  • Leishmania braziliensis (drug effects, enzymology, ultrastructure)
  • Leishmania infantum (drug effects, enzymology, ultrastructure)
  • Leishmaniasis (drug therapy, parasitology)
  • Macrocyclic Compounds (chemistry, pharmacology)
  • Macrophages (drug effects)
  • Mice, Inbred BALB C
  • Microscopy, Electron, Transmission
  • Models, Molecular
  • Polyamines (chemistry, pharmacology)
  • Protozoan Proteins (drug effects, metabolism)
  • Pyrazoles (chemistry, pharmacology)
  • Superoxide Dismutase (drug effects, metabolism)

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