title: Synthesis and biological properties of N2-substituted spin-labeled analogues of actinomycin D.
abstract: We have synthesized N2-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)]actinomycin D And the related 1,2-diaminoethane and 1,3-diaminopropane derivatives and evaluated their biological properties. Binding studies with the spin-labeled actinomycin D analogues and DNA were carried out by using circular dichroism, electron spin resonance, and thermal denaturation. These studies have suggested that the derivatives bind to DNA and that their DNA-binding modes are similar but not identical. Spin-labeled actinomycin D derivatives were less potent in inhibiting Escherichia coli DNA-dependent RNA polymerase reaction than actinomycin D and were less toxic to L1210 cells in vitro than the parent compound. Spin-labeled actinomycin D derivatives were more common than the parent compounds against P-388 leukemia cells in vitro with little or no toxicity.
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D004578:Electron Spin Resonance Spectroscopy; D006358:Hot Temperature; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D009691:Nucleic Acid Denaturation; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D003609:Dactinomycin; D004247:DNA; D012321:DNA-Directed RNA Polymerases