Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis

dc.creatorMelos, Jorge Luiz R. de
dc.creatorSantos, Eduardo Caio Torres
dc.creatorFaiões, Viviane dos S.
dc.creatorCista, Catarina de Nigris Del
dc.creatorSant`Anna, Carlos Maurício R.
dc.creatorSantos, Claudio Eduardo Rodrigues
dc.creatorEchevarria, Aurea
dc.date2016-04-26T17:22:09Z
dc.date2016-04-26T17:22:09Z
dc.date2015
dc.date.accessioned2023-09-26T20:43:53Z
dc.date.available2023-09-26T20:43:53Z
dc.identifierMELOS, 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.
dc.identifier0223-5234
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/13975
dc.identifier10.1016/j.ejmech.2015.09.009
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8862837
dc.descriptionA 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectLeishmania amazonensis
dc.subjectPromastigotes
dc.subjectAmastigotes
dc.subjectThiosemicarbazones
dc.subjectLeishmania
dc.subjectTiossemicarbazonas
dc.titleNovel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis
dc.typeArticle


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