Synthesis and cytotoxic evaluation of combretafurazans.

نویسندگان

  • Gian Cesare Tron
  • Francesca Pagliai
  • Erika Del Grosso
  • Armando A Genazzani
  • Giovanni Sorba
چکیده

Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins embodying a furazan ring (combretafurazans). To achieve this, we have developed a new strategy that exploits the dehydration of vicinal dioximes using the Mitsunobu reaction. Among the advantages of following such a strategy are the mild conditions used for the construction of the diarylfurazan derivatives, allowing for the presence of highly functionalized substrates and deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles.

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عنوان ژورنال:
  • Journal of medicinal chemistry

دوره 48 9  شماره 

صفحات  -

تاریخ انتشار 2005