Photobiological properties of nabumetone (4-[6-methoxy-2-naphthalenyl]-2-butanone), a novel non-steroidal anti-inflammatory and analgesic agent.
The photolability of nabumetone (NB, 1, 4-[6-methoxy-2-naphthalenyl]-2-butanone) and its photobiological properties were studied under aerobic and anaerobic conditions using a variety of in vitro phototoxicity assays: photohemolysis, photoperoxidation of linoleic acid, and photosensitized degradation of histidine and thymine. The photodegradation rate of NB in methanol and phosphate buffered saline (PBS) was enhanced under oxygenated media. NB was phototoxic in vitro. The photohemolysis rate was enhanced by deuterium oxide and inhibited by the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO), butylated hydroxyanisole (BHA), sodium azide (NaN3) and reduced gluthathione (GSH). The induced photoperoxidation of linoleic acid was inhibited significantly by sodium azide and reduced gluthathione. Histidine and thymine were photodegraded by a photosensitized reaction induced by NB. A mechanism involving singlet oxygen, radicals and photoproducts is suggested for the observed photoxicity.
Canudas
N
N
Departamento de Química, Universidad Simón Bolívar, Caracas, Venezuela. ncanudas@usb.ve
Moulinier
J
J
Zamora
D
D
Sánchez
A
A
D000332:Aerobiosis; D000693:Anaerobiosis; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000633:toxicity; D002074:Butanones / Q000737:chemistry* / Q000633:toxicity; D017484:Dermatitis, Phototoxic / Q000097:blood / Q000473:pathology*; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D006461:Hemolysis / Q000187:drug effects; D006639:Histidine / Q000737:chemistry; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000737:chemistry; D000077430:Nabumetone; D010777:Photochemistry; D013056:Spectrophotometry, Ultraviolet; D013941:Thymine / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D008054:Lipid Peroxides; D006639:Histidine; D019787:Linoleic Acid; D000077430:Nabumetone; D013941:Thymine