RESUMO
This paper presents the synthesis of six hydrazones from isatin and 1-morpholinomethyl-isatin and also of their six cooper's complex salts. Their structure was confirmed by the results of the quantitative elemental analysis and by IR, UV-VIS spectral analysis. The biological tests point out that cooper's complex salt of 3-(3'-phenyl-pyridazinylhydrazono)-5-methyl-indoline-2-one (1:2) (VI a) has the smallest toxicity (DMT over 800 mg/kg.w. p.o.), a remarkable anti-inflammatory activity (inhibition 57.1%, IAR 1.1) and also a gastroprotector coefficient of 43.3%. In the mean time, the cooper's complex salt of 3-(3'-p-anisyl-pyridazinyl-hydrazono)-5-methyl-ind oline-2-one (1:2) (VI b) has a gastroprotector coefficient of 76.3% and a lower anti-inflammatory activity than the first derivative (inhibition 36.9%).
Assuntos
Anti-Inflamatórios/síntese química , Isatina/análogos & derivados , Piridazinas/síntese química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Carragenina , Avaliação Pré-Clínica de Medicamentos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Isatina/química , Masculino , Camundongos , Piridazinas/química , Piridazinas/uso terapêutico , Piridazinas/toxicidadeRESUMO
The paper presents a synthesis of six new Mannich bases, five hydrazones derived from 1-piperidino-methyl-5-R-isatin and three copper complex compounds of 3-(3'-R-phenyl-pyridazinil-hydrazone)-indoline-2-ones (R=H, CH3, OCH3). The structure of the new compounds was confirmed by the results of the elementary and spectral analysis. Pharmacodynamic studies indicated that copper complex compounds present effective biological properties. Thus, it can be seen that the experimental carrageenan-induced inflammatory oedema was 58.3% inhibited by the complex V (R=CH3) after oral administration. Antimicrobial tests revealed that only compound V (R=OCH3) shows a moderate antimicrobial activity against the gram-positive and gram-negative bacteria, used in the test.
Assuntos
Hidrazonas/farmacologia , Isatina/análogos & derivados , Bases de Mannich/farmacologia , Animais , Antibacterianos , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/uso terapêutico , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Carragenina , Avaliação Pré-Clínica de Medicamentos , Hidrazonas/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Isatina/farmacologia , Isatina/uso terapêutico , Bases de Mannich/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
This paper presents the synthesis of six hydrazones obtained by treating 5-methyl-isatin or 1-morpholino methyl-5-methyl-isatin with 3-(R-phenyl)-6-hydrazino-pyridazine (R = OCH3, Cl, Br) and two complex combination with copper, derived from 3-(p-anisyl-pyridazinyl)-hydrazone-5-methyl-indoline-2- one. The structure of the new compounds was confirmed by the results of the quantitative elementary and IR, UV-VIS spectral analysis. The biological tests point out that product VI, in which a copper atom binds two molecules of 3-(p-anisyl-pyridazinyl)-hydrazono-5-methyl-indoline-2-one, has a considerable antiinflammatory activity, giving a inflammation inhibition of 39, 6%. All the synthetized compounds have a moderate antimicrobial activity against Candida albicans.