Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/13975
Title: Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis
Authors: Melos, Jorge Luiz R. de
Santos, Eduardo Caio Torres
Faiões, Viviane dos S.
Cista, Catarina de Nigris Del
Sant`Anna, Carlos Maurício R.
Santos, Claudio Eduardo Rodrigues
Echevarria, Aurea
Affilliation: Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil.
Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil.
Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil.
Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil.
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.
Keywords: Leishmania amazonensis
Promastigotes
Amastigotes
Thiosemicarbazones
DeCS: Leishmania
Tiossemicarbazonas
Issue Date: 2015
Publisher: Elsevier
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.
DOI: 10.1016/j.ejmech.2015.09.009
ISSN: 0223-5234
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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