Aspirin-like Molecules that Covalently Inactivate Cyclooxygenase-2
| Autor: | Scott W. Rowlinson, Karen Seibert, Lawrence J. Marnett, Brenda C. Crews, Amit S. Kalgutkar, Carlos Garner |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Indomethacin
Sulfides Pharmacology Dinoprostone Cell Line In vivo Antithrombotic Tumor Cells Cultured medicine Animals Humans Cyclooxygenase Inhibitors Aspirin Binding Sites Multidisciplinary Cyclooxygenase 2 Inhibitors biology Acetylene Prostaglandin D2 Chemistry Macrophages Anti-Inflammatory Agents Non-Steroidal Membrane Proteins Acetylation Biological activity In vitro Rats Isoenzymes Thromboxane B2 Biochemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Rats Inbred Lew Enzyme inhibitor Alkynes Drug Design Colonic Neoplasms Mutagenesis Site-Directed biology.protein Cyclooxygenase Cell Division medicine.drug |
| Zdroj: | Science. 280:1268-1270 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.280.5367.1268 |
| Popis: | Many of aspirin's therapeutic effects arise from its acetylation of cyclooxygenase-2 (COX-2), whereas its antithrombotic and ulcerogenic effects result from its acetylation of COX-1. Here, aspirin-like molecules were designed that preferentially acetylate and irreversibly inactivate COX-2. The most potent of these compounds was o -(acetoxyphenyl)hept-2-ynyl sulfide (APHS). Relative to aspirin, APHS was 60 times as reactive against COX-2 and 100 times as selective for its inhibition; it also inhibited COX-2 in cultured macrophages and colon cancer cells and in the rat air pouch in vivo. Such compounds may lead to the development of aspirin-like drugs for the treatment or prevention of immunological and proliferative diseases without gastrointestinal or hematologic side effects. |
| Databáze: | OpenAIRE |
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