Author | Melos, Jorge Luiz R. de | |
Author | Santos, Eduardo Caio Torres | |
Author | Faiões, Viviane dos S. | |
Author | Cista, Catarina de Nigris Del | |
Author | Sant`Anna, Carlos Maurício R. | |
Author | Santos, Claudio Eduardo Rodrigues | |
Author | Echevarria, Aurea | |
Access date | 2016-04-26T17:22:09Z | |
Available date | 2016-04-26T17:22:09Z | |
Document date | 2015 | |
Citation | MELOS, Jorge Luiz R. de; et al. Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis. European Journal of Medicinal Chemistry, v.103, p.409-417, Oct. 2015. | pt_BR |
ISSN | 0223-5234 | |
URI | https://www.arca.fiocruz.br/handle/icict/13975 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | restricted access | pt_BR |
Title | Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.ejmech.2015.09.009 | |
Abstract | A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16–27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85–98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 μM and 16.40 μM, respectively. The intracellular amastigotes assays showed IC50 = 22.00 μM (22) and 17.00 μM (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase. | pt_BR |
Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil. | pt_BR |
Subject | Leishmania amazonensis | pt_BR |
Subject | Promastigotes | pt_BR |
Subject | Amastigotes | pt_BR |
Subject | Thiosemicarbazones | pt_BR |
DeCS | Leishmania | pt_BR |
DeCS | Tiossemicarbazonas | pt_BR |