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.
Published Web Locationhttps://doi.org/10.1016/j.bmcl.2016.02.028
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.