RESUMO
The purpose of the study was to investigate the in vivo metabolic pathway of 3-oxo-5-benzylidene-6-methyl-(4H)-2-(benzoylmethyl)pyridazine (substrate) in rats. Firstly its potential metabolites, i.e. N-dealkylation, ring scission of pyridazine and aromatic hydroxylation products, were synthesized and then the substrate was given orally (100 mg/kg) to male or female Wistar rats at a dose of 100 mg/kg to body weight. Blood samples were collected at 0, 1, 2, 4, 6 and 8 hours after administration of substrate and blood was centrifuged to obtain serum. The substrate and its potential metabolites were separated using a gradient HPLC method on a reverse phase system. This study revealed that 3-oxo-5-benzylidene-6-methyl-(4H)-2-(benzoylmethyl)pyridazine was not metabolized to the proposed metabolites and was present unchanged in the serum.
Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Piridazinas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/síntese química , Biotransformação , Cateterismo Periférico , Cromatografia Líquida de Alta Pressão , Remoção de Radical Alquila , Feminino , Hidroxilação , Artéria Ilíaca , Masculino , Piridazinas/sangue , Piridazinas/síntese química , Ratos , Padrões de Referência , SoluçõesRESUMO
Two novel series of 4-thiazolidinone derivatives, namely 2-substituted-3-([4-(4-methoxybenzoylamino)benzoyl]amino)-4-thiazolidinones (7a-e) and 2-[4-(4-methoxybenzoylamino)benzoylhydrazono]-3-alkyl-4-thiazolidinones (5a-c) together with 2-[4-(4-methoxybenzoylamino)phenyl]-5-(substituted phenyl)amino-1,3,4-oxadiazoles (6a-c) have been synthesised as title compounds. N(1)-[4-(4-methoxybenzoylamino)benzoyl]-N(2)-substituted methylene hydrazines (3a-e) and 1-[4-(4-methoxybenzoylamino)benzoyl]-4-substituted phenyl thiosemicarbazides (4a-f) were also prepared and used as intermediate to give the title compounds. All synthesised compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv and antimicrobial activities against various bacteria and fungi. Compounds 7a and 7b were found as the most active derivatives demonstrating 90 and 98% inhibition of mycobacterial growth of M. tuberculosis H37Rv in the primary screen at 6.25 microg mL(-1), respectively. However, level II assay revealed that the MIC values were not less than 6.25 microg mL(-1). None of the compounds showed significant antimicrobial activity against the microorganisms used whereas 3a and 7a inhibited the growth of several bacteria and fungi.
