Potential antitumor agents. 56. "Minimal" DNA-intercalating ligands as antitumor drugs: phenylquinoline-8-carboxamides.
A series of isomeric phenylquinoline-8-carboxamides have been synthesized and evaluated as antitumor agents. This configuration is close to the minimum chromophore required for intercalative binding, since the binding mode of the compounds is dependent on the presence and position of the phenyl ring. If the ring is appended at the 4- or 5-position, it cannot lie within the DNA-intercalation site, and the compounds do not intercalate as shown by both unwinding and helix extension assays. In contrast, the 2-, 3-, and 6-phenyl isomers (where the phenyl ring lies coplanar with the quinoline and in the intercalation site) bind by intercalation. Only those isomers that intercalate show in vivo antitumor activity, with the 2-phenyl derivative in particular possessing broad-spectrum activity in both leukemia and solid-tumor assays.
Atwell
G J
GJ
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Bos
C D
CD
Baguley
B C
BC
Denny
W A
WA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism*; D007364:Intercalating Agents / Q000138:chemical synthesis*; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008024:Ligands; D008175:Lung Neoplasms / Q000188:drug therapy; D011804:Quinolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007364:Intercalating Agents; D008024:Ligands; D011804:Quinolines; D004247:DNA