New mono- and bis-intercalating compounds between DNA base pairs.
With the aim to obtain new bis-intercalating agents in DNA a series of compounds was prepared linking two identical tricyclic moieties (two 4,5'-8-trimethylpsoralen (TMP)) or different (one TMP and one pyrido[3,2-b]quinoline) through a hydrocarburic aminated flexible chai. Bis-psoralen-amines as well as psoralen-pyrydoquinolin-amines were obtained. For comparison the corresponding mono-psoralen-amines were also prepared condensing a TMP moiety with various hydrocarburic aminated chains. Melting profiles of the complexes between bis-psoralen-amines or psoralen-pyridoquinolin-amines and DNA evidence two different thermal transitions, which can be correlated with bis-intercalation which takes place, at least in part, inside duplex DNA. On the other hand mono-psoralen-amines evidenced only one thermal transition, in line with mono-intercalation. Bis-intercalating agents complexed with DNA, under UVA irradiation photoconjugate covalently to the macromolecule, even if to a lower extent in comparison with mono-intercalating agents. Moreover these bis-intercalating agents in the photoreaction with DNA form inter-strand cross-links; also in this case bis-intercalating agents are less active than mono-intercalating agents.
Chiarelotto
G
G
Department of Pharmaceutical Sciences, The University.
Ferlin
M G
MG
Vedaldi
D
D
Dall'Acqua
F
F
Rodighiero
G
G
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000032:analysis / Q000187:drug effects* / Q000528:radiation effects; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D010777:Photochemistry; D013050:Spectrometry, Fluorescence; D014466:Ultraviolet Rays
D000588:Amines; D011564:Furocoumarins; D007364:Intercalating Agents; D008024:Ligands; D004247:DNA