Pyridazinopsoralens of wide chemotherapeutic interest

  • Bioorg Med Chem. 2010 Aug 1;18(15):5708-14. doi: 10.1016/j.bmc.2010.06.006.
Lisa Dalla Via  1 ,  Ornella Gia ,  Sebastiano Marciani Magno ,  Alessandra Braga ,  José Carlos González-Gómez ,  Lázaro Guillermo Pérez-Montoto ,  Eugenio Uriarte
Affiliations
  • 1. Department of Pharmaceutical Sciences, University of Padova, Via F Marzolo 5, I-35131 Padova, Italy. [email protected]
PMID: 20615713 DOI: 10.1016/j.bmc.2010.06.006
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.