A CD study of interactions of ellipticine derivatives with DNA. Relations with the in vitro cytotoxicity.
UV-absorption and circular dichroism (CD) experiments showed that ellipticine derivatives may interact with DNA according to 3 possible binding modes depending on their structure and concentration. The first mode concerned intercalation of 1-methyl-9-hydroxyellipticine (1-Me-HE) with its long axis perpendicular to the long axis of base pairs. The same drug was able to bind to external sites (second mode) once the intercalation sites were saturated at high concentration. The third mode illustrated by 1,2-dimethyl-9-hydroxyisoellipticinium (1-Me-isoNMHE), concerned self-stacked molecules interacting at the surface of DNA. Biological significance of these different binding modes was then discussed in connection with in vitro cytotoxic activity of compounds.
Monnot
M
M
Institut Gustave Roussy, PRII, Laboratoire de Biochimie-Enzymologie, URA147 CNRS, U140 INSERM, Villejuif, France.
Mauffret
O
O
Simon
V
V
Lescot
E
E
Psaume
B
B
Saucier
J M
JM
Belehradek
J
J
Fermandjian
S
S
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004611:Ellipticines / Q000737:chemistry* / Q000494:pharmacology; D007939:Leukemia L1210; D051379:Mice; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011067:Poly dA-dT / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D004611:Ellipticines; D011067:Poly dA-dT; D004247:DNA