In vitro effects of bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine) zinc perchlorate monohydrate 4 on the physiology and interaction process of Leishmania amazonensis

dc.creatorSangenito, Leandro S.
dc.creatorRodrigues, Hallana D.
dc.creatorSantiago, Simone O.
dc.creatorBombaça, Ana Cristina S.
dc.creatorMenna-Barreto, Rubem F.S.
dc.creatorReddy, Andrew
dc.creatorBranquinha, Marta H.
dc.creatorVelasco-Torrijos, Trinidad
dc.creatorSantos, André L.S.
dc.date2021-11-12T15:05:15Z
dc.date2021-11-12T15:05:15Z
dc.date2021
dc.date.accessioned2023-09-27T00:13:44Z
dc.date.available2023-09-27T00:13:44Z
dc.identifierSANGENITO, Leandro S. et al. In vitro effects of bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine) zinc perchlorate monohydrate 4 on the physiology and interaction process of Leishmania amazonensis. Parasitology International, v. 84, 102376, p. 1-6, May 2021.
dc.identifier1383-5769
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/49816
dc.identifier10.1016/j.parint.2021.102376
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898733
dc.descriptionDespite the high morbidity, mortality and socio-economic impact, few therapeutic options are available for this disease. To make matters worse, the available molecules have several limitations such as limited efficacy, high cost, side effects and increased resistance. In this context, our group previously synthesized new compounds with anti-leishmania potential being the bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine)zinc perchlorate monohydrate 4 (complex 4) the most promising one. Therefore, this present work revealed some morphological and physiological changes promoted by complex 4 on Leishmania amazonensis promastigotes as well as it was evidenced its potential against intramacrophage amastigotes. Complex 4 promoted a progressive reduction on the promastigotes size and a remarkable increase on the granularity/complexity as judged by flow cytometry. Transmission electron microscopy (TEM) analysis revealed extensive mitochondrial and plasma membrane alterations, although plasma membrane integrity remained. The mitochondrial changes observed by TEM were accompanied by a decrease in the activity of mitochondrial dehydrogenases with increased production of reactive oxygen species. Interestingly, promastigotes also showed changes in lipid metabolism. Besides the very low toxicity to macrophages, complex 4 had a great effect on intramacrophage amastigotes, displaying an IC50 of 3.91 μM. Collectively, the data presented here reinforce the potential of aminopyridyl compounds complexed to zinc against L. amazonensis. Thus, our work serves as a basis for in vivo assays to be designed or even the synthesis of more selective/effective compounds with lower cost.
dc.description2023
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectLeishmania amazonensis
dc.subjectAminopiridil
dc.subjectQuelante de metal
dc.subjectComplexo de zinco
dc.subjectAção anti-Leishmania
dc.subjectLeishmania amazonensis
dc.subjectAminopyridyl
dc.subjectMetal chelator
dc.subjectZinc complex
dc.subjectAnti-Leishmania action
dc.titleIn vitro effects of bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine) zinc perchlorate monohydrate 4 on the physiology and interaction process of Leishmania amazonensis
dc.typeArticle


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