Anti-inflammatory and Anti-allergic Activities of Hydroxylamine and Related Compounds
| Autor: | Masanori Semma, Yoshio Ito, Mitsuo Takayama, Hiromi Kataoka, Kyoko Ishiguro, Shizuyo Horiyama, Toyoshi Katagi, Hisae Oku, Masae Yamaki |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Stereochemistry medicine.drug_class Pharmaceutical Science Hydroxylamine Pharmacology Anti-inflammatory Rats Sprague-Dawley Mice chemistry.chemical_compound Oral administration Acetyl chloride Anti-Allergic Agents medicine Animals Edema Pain Measurement Mice Inbred BALB C biology Chemistry Sodium cyanoborohydride Anti-Inflammatory Agents Non-Steroidal General Medicine Rats Mechanism of action Enzyme inhibitor biology.protein Cyclooxygenase medicine.symptom |
| Zdroj: | Biological and Pharmaceutical Bulletin. 25:1436-1441 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.25.1436 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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