title: Hydroxyurea derivatives of irofulven with improved antitumor efficacy.
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.
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Staake
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
authors.forename: Alisala
authors.initials: A
authors.lastname: Kashinatham
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
authors.forename: Trevor C
authors.initials: TC
authors.lastname: McMorris
authors.affiliation: Department of Pathology, University of California, San Diego, MC 7721, La Jolla, CA 92093-7721, USA.
authors.forename: Leita A
authors.initials: LA
authors.lastname: Estes
authors.affiliation: Department of Pathology, University of California, San Diego, MC 7721, La Jolla, CA 92093-7721, USA. Electronic address: mkelner@ucsd.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kelner
mesh_terms: D000107:Acetylation; D000363:Agaricales / Q000737:chemistry; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C102714:irofulven; C008105:illudin S; D006918:Hydroxyurea
keywords: Analog LP-184; Hydroxyurea; Illudin S; Irofulven; Xenograft