RESUMO
This study aimed at describing the characteristics and properties of seizures induced by cunaniol, a polyacetylenic alcohol isolated from the Clibadium genus, which is ubiquitous in the Amazon biodiversity and its potential use as a convulsant model. Wistar rat behavior was assessed upon cunaniol administration and animals were evaluated for neural activity through electroencephalographic records whereby epidural electrodes were positioned over the motor cortex under cunaniol-elicited seizures and seizure's control using three anticonvulsant agents, namely phenytoin, phenobarbital and diazepam. Cunaniol-induced seizures displayed a cyclic development of electrocorticographic seizures, presenting interictal-like spike and ictal period, which correlates to the behavioral observations and is in line with acute seizures induced by pentylenetetrazole. Cunaniol-elicited seizures were intractable by phenytoin treatment and controlled under the GABAergic activities of phenobarbital and diazepam. The results indicate that the cunaniol-induced changes show characteristics of seizure activity, making this plant compound a suitable animal convulsant model for seizure-related studies that could be used to assist in the development of novel anticonvulsant agents.
Assuntos
Anticonvulsivantes/farmacologia , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Animais , Convulsivantes/farmacologia , Diazepam/farmacologia , Modelos Animais de Doenças , Eletroencefalografia/métodos , Pentilenotetrazol/farmacologia , Fenobarbital/farmacologia , Fenitoína/farmacologia , Ratos , Ratos WistarRESUMO
Chagas disease is a so-called "neglected disease" and endemic to Latin America. Nifurtimox and benznidazole are drugs that have considerable efficacy in the treatment of the acute phase of the disease but cause many significant side effects. Furthermore, in the Chronic Phase its efficiency is reduced and their therapeutic effectiveness is dependent on the type of T. cruzi strain. For this reason, the present work aims to drive basic research towards the discovery of new chemical entities to treat Chagas disease. Differently substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines were synthesized by cyclocondensation of substituted flavones with ethylenediamine and tested as anti-Trypanosoma cruzi candidates. Epimastigotes of the Y strain from T. cruzi were used in this study and the number of parasites was determined in a Neubauer chamber. The most potent diaryldiazepine that reduced epimastigote proliferation exhibited an IC50 value of 0.25 µM, which is significantly more active than benznidazole.
Assuntos
Azepinas/síntese química , Azepinas/farmacologia , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Azepinas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectrofotometria Infravermelho , Tripanossomicidas/químicaRESUMO
Free ortho-hydroxy cinnamate ester derivatives are evaluated in the synthesis of structurally diverse 4-aryl-coumarins via a tandem Heck-Matsuda cyclization reaction. Free phenolic groups were considered incompatible with such a reaction, which usually provide the corresponding diazo dyes. A concise and scalable route employing a ligand-free, Pd-catalyzed Heck-Matsuda arylation under aerobic conditions for the preparation of (R)-Tolterodine in high overall yield and ee is also presented.
Assuntos
Compostos Benzidrílicos/síntese química , Cinamatos/química , Cumarínicos/síntese química , Cresóis/síntese química , Fenilpropanolamina/síntese química , Compostos Benzidrílicos/química , Catálise , Cumarínicos/química , Cresóis/química , Ciclização , Ésteres , Estrutura Molecular , Paládio/química , Fenilpropanolamina/química , Estereoisomerismo , Tartarato de TolterodinaRESUMO
ß,ß-Disubstituted α,ß-unsaturated esters may serve as valuable derivatives for the preparation of other highly functionalized systems found in many natural products and marketed drugs. The stereoselective synthesis of unsymmetrical ß,ß-diarylacrylate compounds possessing two similar aromatic groups remains a substantial challenge. A simple and convenient stereoselective protocol for the preparation of ß,ß-disubstituted acrylates via a Heck-Matsuda reaction is reported. Good to high yields were accomplished by a "ligand-free" Pd-catalyzed arylation reaction of cinnamate esters with arenediazonium tetrafluoroborates. Both electron-deficient and electron-rich arenediazonium salts could be employed as arylating reagents, and cinnamate esters were generally more reactive when substituted with an electron-donating group. The overall methodology is highly stereoselective, and this attribute was taken advantage of in the asymmetric Cu-catalyzed 1,4 reduction reaction to provide ß,ß-diarylpropanoates in high enantioselectivities. The synthesis of a 3-aryl indole and a chiral 4-aryl-2-quinolone from ß,ß-diarylacrylates was achieved by cyclization in the presence of a diphosphine ligated CuH catalyst. A convenient route for the asymmetric formal synthesis of the psychoactive compound (-)-Indatraline is also presented.