The dicationic derivatives of DBTAA: Interactions with DNA/RNA and antiproliferative effects on human cell lines.
Three dibenzotetraaza[14]annulenes non-covalently interacted with double-stranded DNA and RNA by mixed minor groove and/or intercalative binding mode. Observed interactions were strongly dependent on the steric exposure of positive charges and the length of the linkers of studied compounds as well as on the secondary structure and basepair composition of DNA/RNA. Compound 2 showed pronounced selectivity toward dA-dT-rich sequences and binding mode switch from dominant minor groove binding to ds-DNA to dominant intercalation into ds-RNA. Antiproliferative effect of studied compounds on human tumor and normal cell lines was in good agreement with the strength of observed interactions with DNA/RNA.
Stojković
Marijana Radić
MR
Laboratory for Supramolecular and Nucleoside Chemistry, Division of Organic Chemistry and Biochemistry, Ruder Bosković Institute, PO Box 180, HR-10002 Zagreb, Croatia.
Piantanida
Ivo
I
Kralj
Marijeta
M
Marjanović
Marko
M
Zinić
Mladen
M
Pawlica
Dariusz
D
Eilmes
Julita
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020029:Base Pairing; D001665:Binding Sites; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism*; D005290:Ferric Compounds; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D012330:RNA, Double-Stranded / Q000378:metabolism*
D000970:Antineoplastic Agents; D002413:Cations, Divalent; D003432:Cross-Linking Reagents; D005290:Ferric Compounds; D007364:Intercalating Agents; D012330:RNA, Double-Stranded; C444506:dibenzotetraaza(14)annulene-Fe(III) complex; D004247:DNA