The DNA-association and biological activity of a new bis(14-thiadaunomycin).
A new bis-daunomycin has been synthesized and characterized by 13C-n.m.r. and reversed-phase h.p.l.c. The compound was found to be highly self-associated in aqueous solution and to bis-intercalate into DNA with a residence time about 200-fold greater than the parent compound daunomycin. Although the bis-daunomycin and its parent congener were taken up by V79 Chinese hamster ovarian leukaemia cells to similar extents, the cytotoxicity of the former was considerably lower. The possible in vivo relationship between DNA binding affinity and cytotoxicity is discussed.
Skorobogaty
A
A
Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.
Brownlee
R T
RT
Chandler
C J
CJ
Kyratzis
I
I
Phillips
D R
DR
Reiss
J A
JA
Trist
H
H
D000818:Animals; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D007364:Intercalating Agents; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility; D013329:Structure-Activity Relationship
D007364:Intercalating Agents; C056504:bis(14-thiadaunomycin); D003630:Daunorubicin