The synthesis, stability and biological activity of bis-intercalating bis-daunomycin hydrazones Academic Article uri icon

abstract

  • The synthesis of a series of bis-daunomycin hydrazones (5a-g)--all moderately stable at 37 degrees C, pH 6.8, with a half-life of approximately 30 h--is reported. Under a pulse exposure of 2 h they exhibited growth inhibition of mouse L1210 cells, and were 2-3 fold more active than daunomycin. Under continuous exposure growth inhibition conditions with human colon cell lines (HT-29 and HCT-8) they hydrolysed to daunomycin and a partially hydrolysed mono-derivative of daunomycin, and there was no apparent increase in activity over that of the parent anthracycline. Their rate of hydrolysis was observed to increase rapidly with decreasing pH.

publication date

  • January 1, 1990