NEW MONO-INTERCALATING 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 pyrido3 ,2-b!quinoline) through a hydrocarburic aminated flexible chai. Bis-ps oralen-amines as well as psoralen-pyrydoquinolin-amines were obtained. For comparison the corresponding mono-psoralen-amines were also prepa red condensing a TMP moiety with various hydrocarburic aminated chains . Melting profiles of the complexes between bis-psoralen-amines or pso ralen-pyridoquinolin-amines and DNA evidence two different thermal tra nsitions, which can be correlated with bis-intercalation which takes p lace, at least in part, inside duplex DNA. On the other hand mono-psor alen-amines evidenced only one thermal transition, in line with mono-i ntercalation. Bis-intercalating agents complexed with DNA, under UVA i rradiation 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 inte r-strand cross-links, also in this case bis-intercalating agents are l ess active than mono-intercalating agents.