title: Nature of toxicity for chick embryo fibroblast cells of coumermycin A1 and its physico-chemical interactions with protein and nucleic acid.
abstract: The results reported in this paper describe the effects produced by the antibiotic Coumermycin A1 (CA1) on survival and metabolism of chick embryo fibroblast cells (CEF), and give a clue to the understanding of its toxicity. The drug acts primarily at the level of DNA and RNA synthetic enzymes; no effect on DNA superstructure is detectable at doses at which cytotoxicity is pronounced. A spectroscopic approach produced evidence that CA1 binds to DNA, RNA, chromatin components such as histones and to a structurally unrelated protein such as bovine serum albumin. Furthermore, CA1 behaves like a pure non-competitive inhibitor of lactic dehydrogenase, a ubiquitous enzyme not involved in nucleic acid metabolism. The interaction of CA1 with a wide range of macromolecules playing different biological roles is certainly relevant to its activity and adds a new insight into the mechanism of action of this antibiotic. These observations are also discussed in the light of the alleged role of CA1 as a specific inhibitor of DNA topoisomerase in eukaryotic cells.
mesh_terms: D049933:Aminocoumarins; D000818:Animals; D002642:Chick Embryo; D003374:Coumarins / Q000633:toxicity; D004257:DNA Polymerase II / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008433:Mathematics; D014176:Protein Biosynthesis / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis*; D012319:RNA Polymerase II / Q000378:metabolism; D013053:Spectrophotometry
chemical_list: D049933:Aminocoumarins; D003374:Coumarins; D012313:RNA; D007770:L-Lactate Dehydrogenase; D012319:RNA Polymerase II; D004257:DNA Polymerase II; C004628:coumermycin