title: Pyridazinopsoralens of wide chemotherapeutic interest.
abstract: The synthesis of new 6,10-dimethylpyridazino[4,5-h]psoralens, carrying no (4), one (5), or two (6-9) dialkylaminoalkylcarboxamide side chains on the pyridazine ring is reported. All compounds exert a significant photoantiproliferative activity. Moreover, the derivatives characterised by the protonable side chains show a notable cytotoxicity in the dark. The investigation on the mechanism of action demonstrated the capacity to intercalate into DNA base pairs and to inhibit the relaxation activity of topoisomerase II.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, Via F Marzolo 5, I-35131 Padova, Italy. lisa.dallavia@unipd.it
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Ornella
authors.initials: O
authors.lastname: Gia
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Marciani Magno
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braga
authors.forename: José Carlos
authors.initials: JC
authors.lastname: González-Gómez
authors.forename: Lázaro Guillermo
authors.initials: LG
authors.lastname: Pérez-Montoto
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
mesh_terms: D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D011564:Furocoumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011724:Pyridazines / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors; D014466:Ultraviolet Rays
chemical_list: D004791:Enzyme Inhibitors; D011564:Furocoumarins; D007364:Intercalating Agents; D011724:Pyridazines; D059005:Topoisomerase II Inhibitors; C062482:pyridazine; D004250:DNA Topoisomerases, Type II