Photolytic degradation of benorylate: effects of the photoproducts on cultured hepatocytes.
The photodegradation of benorylate [4'-(acetamido)phenyl-2-acetoxybenzoate], a drug frequently used in rheumatoid arthritis therapy, has been examined under different sets of experimental conditions. Several photoproducts have been isolated and identified on the basis of their IR, NMR, and MS spectra. The most significant photochemical process is the photo-Fries rearrangement of benorylate, leading to 5-acetamido-2'-acetoxy-2-hydroxybenzophenone (1). This compound undergoes a rapid transacylation to the isomeric 5'-acetamido-2'-acetoxy-2-hydroxybenzophenone (2). A primary culture of rat hepatocytes has been used to evaluate the possible toxicity of these two benzophenones, keeping in mind the following criteria: leakage of cytosolic enzymes, attachment index to culture plates, gluconeogenesis from lactate and fructose, glycogen balance, and albumin synthesis. At the concentrations assayed, neither of the two major photoproducts of benorylate (benzophenones 1 and 2) had significant toxic effects on liver cells in culture.
D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001577:Benzophenones / Q000302:isolation & purification / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D005943:Gluconeogenesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008027:Light; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010782:Photolysis; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000302:isolation & purification / Q000494:pharmacology* / Q000528:radiation effects; D013057:Spectrum Analysis
D000418:Albumins; D001577:Benzophenones; D012459:Salicylates; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases