Cytoxicity of [(5,6-dichloro-9a-n-propyl-2,3,9,9a-tetrahydro-3-oxo-1H fluoren-7-yl)oxy]acetic acid, an agent known to reduce brain edema.
A known agent, [(5,6-dichloro-9a-n-propyl-2,3,9,9a-tetrahydro-3-oxo-1H fluoren-7-yl)oxy]acetic acid, which blocks brain edema, was also shown to be a potent cytotoxic agent in leukemia cells. The major site of action of the agents appears to be in the de novo purine synthetic pathway in L1210 leukemic cells. Both PRPP amido transferase and IMP dehydrogenase activities were suppressed by the agent. The inhibition of both regulatory enzymes of the pathway along with the reduction of dihydrofolate reductase activity would account for the observed suppression of DNA and RNA syntheses and subsequent cancer cell death.
Hall
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IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina-CH 27599-7360, USA.
Wyrick
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D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011687:Purines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000085:Acetates; D011687:Purines