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.
Authors	P 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
Journal	Parasitology (Parasitology) Vol. 141 Issue 8 Pg. 1031-43 (Jul 2014) ISSN: 1469-8161 [Electronic] England
PMID	24636142 (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)

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