| Author | Tabélé, Clémence | |
| Author | Faiões, Viviane dos S. | |
| Author | Grimaud, Fabien | |
| Author | Santos, Eduardo Caio Torres | |
| Author | Khoumeri, Omar | |
| Author | Curti, Christophe | |
| Author | Vanelle, Patrice | |
| Access date | 2018-09-18T16:27:04Z | |
| Available date | 2018-09-18T16:27:04Z | |
| Document date | 2018 | |
| Citation | TABÈLÉ, Clémence et al. Original antileishmanial hits: Variations around amidoximes. European Journal of Medicinal Chemistry, v. 148, p. 154-164, Feb. 2018. | pt_BR |
| ISSN | 0223-5234 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/28868 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Citotoxicidade in vitro | pt_BR |
| Subject in Portuguese | Antileishemanial | pt_BR |
| Subject in Portuguese | Atividade antiprotozoária in vitro | pt_BR |
| Subject in Portuguese | Amidoximas | pt_BR |
| Subject in Portuguese | modulação de fármacos | pt_BR |
| Title | Original antileishmanial hits: Variations around amidoximes | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1016/j.ejmech.2018.02.029 | |
| Abstract | In continuation to our previous findings on amidoximes' antiparasitic activities, a new series of 23 original derivatives was designed and obtained by convergent synthesis. First, new terminal alkenes were synthesized by cross-coupling reaction. Then, cyclization was performed between terminal alkenes and β-ketosulfones using manganese(III) acetate reactivity. Twenty-three amidoximes were tested for their in vitro activity against Leishmania amazonensis promastigotes and their toxicity on murine macrophages. Seven of the tested compounds exhibited an antileishmanial activity at lower than 10 μM with moderate to low toxicity. Six of these molecules showed activity at lower than 10 μM against promastigotes and toxicity at higher than 50 μM were selected and evaluated for their activity against intracellular Leishmania amazonensis amastigotes. Modulating chemical substituents in position 2 of dihydrofuran highly influenced their antileishmanial activities. The introduction of a methyl or trifluoromethyl group on the benzene ring of the benzyl group had a positive influence on activity without significantly increasing toxicity (52, 59, 60). | pt_BR |
| Affilliation | Aix Marseille Université. Laboratoire de Pharmaco-Chimie Radicalaire. Faculté de Pharmacie. 27 Boulevard Jean Moulin. Marseille, France. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Aix Marseille Université. Laboratoire de Pharmaco-Chimie Radicalaire. Faculté de Pharmacie. 27 Boulevard Jean Moulin. Marseille, France. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Aix Marseille Université. Laboratoire de Pharmaco-Chimie Radicalaire. Faculté de Pharmacie. 27 Boulevard Jean Moulin. Marseille, France. | pt_BR |
| Affilliation | Aix Marseille Université. Laboratoire de Pharmaco-Chimie Radicalaire. Faculté de Pharmacie. 27 Boulevard Jean Moulin. Marseille, France. | pt_BR |
| Affilliation | Aix Marseille Université. Laboratoire de Pharmaco-Chimie Radicalaire. Faculté de Pharmacie. 27 Boulevard Jean Moulin. Marseille, France. | pt_BR |
| Subject | Amidoximes | pt_BR |
| Subject | Dihydrofuran | pt_BR |
| Subject | Manganese(III) acetate | pt_BR |
| Subject | Pharmacomodulation | pt_BR |
| Subject | Cytotoxicity in vitro | pt_BR |
| Subject | Antiprotozoan activity in vitro | pt_BR |
| Subject | antileishmanial hits | pt_BR |
| Embargo date | 2030-01-01 | |
