Interaction of ellipticine and an indolo[2,3b]-quinoxaline derivative with DNA and synthetic polynucleotides.
The non-covalent DNA interaction of the anticancer drug ellipticine (Scheme I, 1a) as well as an indolo[2,3-b]-quinoxaline derivative (Scheme I, 3b) with a dimethylaminoethyl side chain has been studied by light absorption, linear dichroism (LD) and fluorescence. Compound 3b (Scheme I) has antitumorigenic as well as antiviral activity. Both compounds bind to DNA or synthetic polynucleotides such as poly(dA-dT).(dA-dT) and poly(dG-dC).(dG-dC) by intercalation. In contrast to ellipticine, compound 3b (Scheme I) exhibits a significant binding specificity for alternating AT sequences. Its fluorescence is strongly enhanced in AT sequences and quenched in GC sequences. Fluorescence titrations evaluated as Scatchard plots show that both ellipticine and compound 3b (Scheme I) bind to the nucleic acids according to a non-cooperative neighbor exclusion model.
Zegar
I
I
Department of Biophysics, University of Stockholm, Sweden.
Gräslund
A
A
Bergman
J
J
Eriksson
M
M
Nordén
B
B
D000470:Alkaloids / Q000138:chemical synthesis; D004247:DNA; D004611:Ellipticines / Q000138:chemical synthesis; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis; D007700:Kinetics; D011067:Poly dA-dT; D011089:Polydeoxyribonucleotides; D011810:Quinoxalines / Q000138:chemical synthesis; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D000470:Alkaloids; D004611:Ellipticines; D007202:Indicators and Reagents; D007211:Indoles; D011089:Polydeoxyribonucleotides; D011810:Quinoxalines; C034192:ellipticine; C016681:poly(dG).poly(dC); C062268:6-(2-dimethylaminoethyl)-6H-indolo(2,3-b)-quinoxaline; D011067:Poly dA-dT; D004247:DNA