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RESEARCH PRODUCT
In vitro leishmanicidal activity of pyrazole-containing polyamine macrocycles which inhibit the Fe-SOD enzyme of Leishmania infantum and Leishmania braziliensis species
Pilar NavarroClotilde MarínRamón Gutiérrez-sánchezFernando Gómez-contrerasManuel Sánchez-morenoMaría J. R. YuntaFrancisco OlmoMaría José RosalesEnrique García-españaInmaculada Ramírez-macíassubject
Models MolecularLeishmanicidal activityErythrocytesMacrocyclic CompoundsAntioxidantCell Survivalmedicine.medical_treatmentAntiprotozoal AgentsProtozoan ProteinsBiologyLeishmania braziliensisCell LinePolyamine macrocyclechemistry.chemical_compoundMicroscopy Electron TransmissionIron superoxide dismutasePolyaminesmedicineAnimalsHumansLeishmania infantumCytotoxicityLeishmaniasischemistry.chemical_classificationMice Inbred BALB CSuperoxide DismutaseMacrophagesbiology.organism_classificationLeishmania braziliensisIn vitroInfectious DiseasesEnzymechemistryBiochemistryCell culturePyrazolePyrazolesFemaleAnimal Science and ZoologyParasitologyLeishmania infantumPolyaminedescription
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. © Cambridge University Press 2014.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 | Parasitology |