Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/15824
Title: Assessment of Leishmanicidal and Trypanocidal activities of Aliphatic Diamine derivatives
Authors: Yamanaka, Celina N.
Giordani, Raquel B.
Rezende, Celso O.
Eger, Iriane
Kessler, Rafael Luis
Tonini, Maiko L.
Moraes, Milene H. de
Araújo, Debora P.
Zuanazzi, Jose A.
Almeida, Mauro V. de
Steindel, Mario
Affilliation: Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Natal, RN, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Química. Juiz de Fora, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil. / Universidade do Vale do Itajaí. Centro de Ciências da Saúde. Itajaí, SC, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.
Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, Brasil.
Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Química. Juiz de Fora, MG, Brasil.
Universidade Federal do Rio Grande do Sul. Faculdade de Farmácia. Porto Alegre, RS, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Química. Juiz de Fora, MG, Brasil.
Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, Brasil.
Abstract: Leishmanicidal and trypanocidal activity of seventeen lipophilic diamines was evaluated in vitro against Leishmania braziliensis, L. chagasi, and Trypanosoma cruzi. Twelve compounds presented anti-Leishmania and six showed anti-T. cruzi amastigote activity. Compound 14 (N-tetradecyl-1,4-butanediamine) was the most active against both L. braziliensis (IC50 = 2.6 μm) and L. chagasi (IC50 = 3.0 μm) which showed a selectivity index (SI) >100. N-decyl-1,6-hexanediamine (compound 9) presented an IC50 = 1.6 μm and SI >187 and was over six times more potent than the reference drug benznidazole against T. cruzi. Treatment of infected or uninfected macrophages with compounds 9 and 14 did not induce significant TNFα and NO production. Four compounds (15, 16, 22, and 23) inhibited 78.9%, 77.7%, 83.7%, and 70.1% of rTRLb activity, respectively, and compound 23 inhibited 73.3% of rTRTc activity at 100 μm. A concentration-dependent effect on mitochondrial membrane depolarization was observed in T. cruzi epimastigotes treated with compound 9, suggesting this mechanism may be involved in the trypanocidal effect. On the contrary, in L. braziliensis promastigotes treated with compound 14, no mitochondrial depolarization was observed. Our results demonstrate that N-decyl-1,6-hexanediamine and N-tetradecyl-1,4-butanediamine are promising molecules for the development of novel leading compounds against T. cruzi and Leishmania spp., particularly given a possible alternative mechanism of action.
Keywords: aliphatic diamines
Leishmania braziliensis
Leishmania chagasi
leishmanicidal and trypanocidal activity
Trypanosoma cruzi
DeCS: Diaminas
Leishmania infantum
Tripanossomicidas
Issue Date: 2013
Publisher: David Selwood
Citation: YAMANAKA, Celina N. et al. Assessment of Leishmanicidal and Trypanocidal activities of Aliphatic Diamine derivatives. Chem. Biol. Drug. Des, n. 82, p. 697–704, 2013.
ISSN: 1747-0277
Copyright: open access
Appears in Collections:PR - ICC - Artigos de Periódicos

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