9-Octadecynoic acid: a novel DNA binding agent.
A novel bioassay was developed to permit the identification of cytotoxic natural principles that bind to DNA. A hexane extract of Schoepfia californica cytotoxic to cultured KB cells displayed much less cytotoxic potential when the culture medium contained exogenously added calf thymus DNA. Fractionation of the extract afforded a purified principle shown to be 9-octadecynoic acid, an 18-carbon, unbranched acetylenic fatty acid. 9-Octadecynoic acid had an apparent DNA dissociation constant of 1.8 mM; it inhibited topoisomerase I mediated DNA filter binding but did not inhibit the DNA topoisomerase I mediated relaxation of a supercoiled plasmid DNA. The fatty acid was weakly inhibitory to DNA polymerase alpha. 9-Octadecynoic acid possesses none of the structural characteristics of known DNA binding molecules and may bind to DNA by some novel mechanism.
Berry
D E
DE
Department of Biomolecular Discovery, Smith Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Chan
J A
JA
MacKenzie
L
L
Hecht
S M
SM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000480:Alkynes; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004257:DNA Polymerase II / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000187:drug effects; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D007624:KB Cells / Q000166:cytology / Q000187:drug effects
D000480:Alkynes; D005231:Fatty Acids, Unsaturated; C066014:9-stearolic acid; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D004247:DNA; D004257:DNA Polymerase II; D004264:DNA Topoisomerases, Type I