A new series of ellipticine derivatives (1-(alkylamino)-9-methoxyellipticine). Synthesis, DNA binding, and biological properties.
A new series of ellipticine derivatives, 1-(alkylamino)-5,11-dimethyl-9-methoxy-6H-pyrido[4,3-b]carbazoles, were synthesized as potential DNA intercalating antitumor drugs. The structure of these compounds were confirmed by 1H NMR spectroscopy and mass spectrometry. These compounds are able to bind to DNA with an affinity of about 10(6) M-1, and their intercalating characteristics (lengthening and unwinding of DNA) depend upon the length of the chain in position 1. The cytotoxicities of these compounds on L1210 and NIH-3T3 cells are quite similar, and fluorescence techniques showed that the compounds are localized mainly in the cytoplasmic granules of the cells. One of these compounds appears to show a very high antitumor activity (equivalent to the more active known ellipticine analogues: 10-[[gamma-(diethylamino)propyl]amino]-6-methyl-5H- pyrido[3',4':4,5]pyrollo[2,3-g]isoquinoleine (BD40), 1-[[gamma-(diethylamino)propyl]amino]-9-methoxyellipticine (BD84) and 2-[beta-(diethylamino)ethyl]-9-hydroxyellipticinium chloride (DEAE).
Larue
L
L
CNRS (LA 147), Institut Gustave Roussy, Villejuif, France.
Rivalle
C
C
Muzard
G
G
Paoletti
C
C
Bisagni
E
E
Paoletti
J
J
D000470:Alkaloids; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004611:Ellipticines / Q000031:analogs & derivatives* / Q000378:metabolism; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D007939:Leukemia L1210 / Q000473:pathology; D007941:Leukemia P388 / Q000473:pathology; D008856:Microscopy, Fluorescence; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000970:Antineoplastic Agents; D004611:Ellipticines; D007364:Intercalating Agents; C034192:ellipticine; D004247:DNA