1. Hydroxyurea derivatives of irofulven with improved antitumor efficacy
- Author
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Michael J. Kelner, Leita A. Estes, Michael D. Staake, Trevor C. McMorris, and Alisala Kashinatham
- Subjects
0301 basic medicine ,Medicinal & Biomolecular Chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Pharmacology ,Sesquiterpene ,Biochemistry ,Cell Line ,Mice ,Medicinal and Biomolecular Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Therapeutic index ,In vivo ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Irofulven ,Animals ,Humans ,Hydroxyurea ,Molecular Biology ,Antineoplastic Agents, Alkylating ,Inbred BALB C ,Polycyclic Sesquiterpenes ,Mice, Inbred BALB C ,Tumor ,biology ,Xenograft ,Organic Chemistry ,Omphalotus illudens ,Acetylation ,Pharmacology and Pharmaceutical Sciences ,biology.organism_classification ,Alkylating ,In vitro ,Illudin ,Acetic anhydride ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Illudin S ,Molecular Medicine ,Agaricales ,Sesquiterpenes ,Analog LP-184 - 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.
- Published
- 2015