HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

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

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.
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
Topics
  • 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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: