RESUMO
The anti-inflammatory activities of several novel oximes and O-acyl oximes that we synthesized have been reported based on carrageenan-induced rat foot-pad swelling assay and histamine-induced rat vascular permeability assay. A cyclooxygenase (COX)-1 inhibitory effect has also been reported for 4'-piperidinoacetophenone and 4'-morpholinoacetophenone oximes and their O-acyl derivatives. To further search for more effective non-steroidal anti-inflammatory or anti-allergic drugs, 1-hydroxylamino-1-(4'-piperidinophenyl) ethane (P-HA) and 1-hydroxylamino-1-(4'-morpholinophenyl) ethane (M-HA) were synthesized from the corresponding oximes with sodium cyanoborohydride, and N,O-diacetyl hydroxylamines (P-HA-Ac and M-HA-Ac) were prepared from these hydroxylamines using acetyl chloride. These hydroxylamines and N,O-diacetyl hydroxylamines clearly exhibited inhibitory effects on mouse carrageenan-induced foot-pad swelling induced by oral administration (150, 37.5 mg/kg). An oral dose of P-HA-Ac (150 mg/kg) significantly inhibited the mouse anaphylactic reaction to ovalbumin measured by the abdominal wall (AW) method. Percutaneous administration of P-HA and M-HA significantly inhibited 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reaction (type IV) in mice at a dose of 0.5 and 0.1 mg/ear, respectively. All tested hydroxylamines and N,O-diacetyl hydroxylamines clearly inhibited both COX-1 and COX-2 enzyme activities with IC(50) values of 1.9-28.7 and 1.6-2.9 micro M against COX-1 and COX-2, respectively. Hydroxylamines (P-HA and M-HA) also showed a 5-lipoxygenase inhibitory effect.
Assuntos
Antialérgicos/química , Anti-Inflamatórios não Esteroides/química , Hidroxilamina/química , Hidroxilamina/farmacologia , Animais , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Edema/tratamento farmacológico , Edema/fisiopatologia , Hidroxilamina/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Ratos , Ratos Sprague-DawleyRESUMO
Hydroxylamines gradually undergo oxidation to their oximes on being dissolved in organic solvent (e.g. methanol). This phenomenon was followed by (1)H-NMR and liquid chromatography-mass spectrometry (LC-MS). The oxidation rate was estimated from the peak area observed on the mass chromatogram at the protonated molecule or fragment ion on LC-atmospheric pressure chemical ionization (APCI)-MS. The results showed that the oxidation rate of hydroxylamines depended on the solvent type.
Assuntos
Hidroxilaminas/química , Calibragem , Clorofórmio , Cromatografia Líquida , Cetonas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Oxirredução , SolventesRESUMO
The CHCl3-soluble part (HJ) of the MeOH extract from Hypericum japonicum afforded new bisxanthones, jacarelhyperols A (1) and B (2). The structures were elucidated by spectral methods. These compounds and HJ showed significant inhibitory effects against PAF-induced hypotension by an in vivo evaluation method, which can reveal the pharmacological action of the test material.