Hydroxyurea derivatives of irofulven with improved antitumor efficacy

Bioorg Med Chem Lett. 2016 Apr 1;26(7):1836-8. doi: 10.1016/j.bmcl.2016.02.028. Epub 2016 Feb 13.


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.

Keywords: Analog LP-184; Hydroxyurea; Illudin S; Irofulven; Xenograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Agaricales / chemistry
  • Animals
  • Antineoplastic Agents, Alkylating / chemistry*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Cell Line, Tumor
  • Humans
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / pharmacology
  • Hydroxyurea / therapeutic use*
  • Mice, Inbred BALB C
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes / therapeutic use*


  • Antineoplastic Agents, Alkylating
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • irofulven
  • illudin S
  • Hydroxyurea