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Hydroxyurea derivatives of irofulven with improved antitumor efficacy.

  • Author(s): Staake, Michael D
  • Kashinatham, Alisala
  • McMorris, Trevor C
  • Estes, Leita A
  • Kelner, Michael J
  • et al.
Abstract

Irofulven is a semi-synthetic derivative of Illudin S, a toxic sesquiterpene isolated from the mushroom Omphalotus illudens. Irofulven has displayed significant antitumor activity in various clinical trials but displayed a limited therapeutic index. A new derivative of irofulven was prepared by reacting hydroxyurea with irofulven under acidic conditions. Acetylation of this new compound with acetic anhydride produced a second derivative. Both of these new derivatives displayed significant antitumor activity in vitro and in vivo comparable to or exceeding that of irofulven.

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