Hydroxyurea derivatives of irofulven with improved antitumor efficacy
Michael D Staake1, Alisala Kashinatham1, Trevor C McMorris1
1Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
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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