Pyridazinopsoralens of wide chemotherapeutic interest.
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.
Dalla Via
Lisa
L
Department of Pharmaceutical Sciences, University of Padova, Via F Marzolo 5, I-35131 Padova, Italy. lisa.dallavia@unipd.it
Gia
Ornella
O
Marciani Magno
Sebastiano
S
Braga
Alessandra
A
González-Gómez
José Carlos
JC
Pérez-Montoto
Lázaro Guillermo
LG
Uriarte
Eugenio
E
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
D004791:Enzyme Inhibitors; D011564:Furocoumarins; D007364:Intercalating Agents; D011724:Pyridazines; D059005:Topoisomerase II Inhibitors; C062482:pyridazine; D004250:DNA Topoisomerases, Type II