Staake Michael D, Kashinatham Alisala, McMorris Trevor C, Estes Leita A, Kelner Michael J
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
Department of Pathology, University of California, San Diego, MC 7721, La Jolla, CA 92093-7721, USA.
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.
艾罗弗芬是伊利丁S的半合成衍生物，伊利丁S是一种从真菌密环菌中分离出的有毒倍半萜。艾罗弗芬在各种临床试验中已显示出显著的抗肿瘤活性，但治疗指数有限。通过在酸性条件下使羟基脲与艾罗弗芬反应制备了一种艾罗弗芬的新衍生物。用乙酸酐对该新化合物进行乙酰化反应产生了第二种衍生物。这两种新衍生物在体外和体内均显示出显著的抗肿瘤活性，与艾罗弗芬相当或超过艾罗弗芬。
