The synthesis, stability and biological activity of bis-intercalating bis-daunomycin hydrazones.
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.
Phillips
D R
DR
Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.
Baguley
B C
BC
Brownlee
R T
RT
Cacioli
P
P
Chandler
C J
CJ
Kyratzis
I
I
Reiss
J A
JA
Scourides
P A
PA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008968:Molecular Conformation; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006835:Hydrazones; D007364:Intercalating Agents; D003630:Daunorubicin