RESUMO
The synthesis of a series of pentadienoic and hexadienoic acid derivatives is reported. These compounds were tested as inhibitors of 5-lipoxygenase (5 LO) and cyclooxygenase (CO) in vitro and as inhibitors of arachidonic acid (AA) induced ear edema in mice in vivo. Their potency is compared with that of the standard inhibitors nafazatrom, BW 755C, NDGA, KME4, quercetine, and L 652,243. The most potent compound in vivo, diethyl 2-hydroxy-5-(ethylthio)-2(Z),4(Z)-hexadienedioate (20) inhibited AA-induced ear edema when administered topically or orally, with an ED50 value of 0.01 mg/ear and 20 mg/kg, respectively. Among the standard compounds tested, L 652,243 was the most active compound in this test with an ED50 value of 0.01 mg/ear and 1 mg/kg po, but unlike this compound, 20 is a selective inhibitor of 5-LO (IC50 = 2 microM) without any significant activity against CO (IC50 greater than 50 microM). Most of the other compounds in this series are also selective 5-LO inhibitors.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Ácidos Graxos Insaturados/farmacologia , Inibidores de Lipoxigenase , Ácido Sórbico/análogos & derivados , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Bioensaio , Relação Dose-Resposta a Droga , Edema/prevenção & controle , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/síntese química , Ácidos Graxos Insaturados/química , Camundongos , Ácido Sórbico/administração & dosagem , Ácido Sórbico/síntese química , Ácido Sórbico/química , Ácido Sórbico/farmacologia , Relação Estrutura-AtividadeRESUMO
Reaction of 1,5-anhydro-4-O-benzoyl-2,3,6-trideoxy-3-C-methyl-3-trifluoro-acetami no-L-lyxo-hex-1-enitol with daunomycinone in the presence of anhydrous toluene-p-sulfonic acid in benzene, followed by removal of the N- and O-protecting groups under mild conditions, gave 3'-C-methyldaunorubicin. The antitumor activity of the new anthracycline glycoside has been evaluated.
Assuntos
Antineoplásicos/síntese química , Daunorrubicina/análogos & derivados , Animais , Daunorrubicina/síntese química , Daunorrubicina/uso terapêutico , Doxorrubicina/uso terapêutico , Resistência a Medicamentos , Leucemia L1210/tratamento farmacológico , Leucemia P388/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Camundongos , Ensaio Tumoral de Célula-TroncoRESUMO
14-diethoxyacetoxy daunorubicin (R.P. 33 921) was chosen among a series of new daunorubicin analogues. Its preparation from daunorubicin and its biological activities are described. It displays an antitumoral activity in mice with a better chemotherapeutic index than daunorubicin and doxorubicin.
