Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1)

  • J Med Chem. 2002 Jan 17;45(2):529-32. doi: 10.1021/jm0102856.
Deniz Tasdemir  1 ,  Robert Mallon ,  Michael Greenstein ,  Larry R Feldberg ,  Steven C Kim ,  Karen Collins ,  Donald Wojciechowicz ,  Gina C Mangalindan ,  Gisela P Concepción ,  Mary Kay Harper ,  Chris M Ireland
Affiliations
  • 1. Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
PMID: 11784156 DOI: 10.1021/jm0102856
Abstract

Raf/MEK-1/MAPK cascade inhibitor activity-directed fractionation of the Sponge Stylissa massa afforded eight known alkaloids: aldisine (1), 2-bromoaldisine (2), 10Z-debromohymenialdisine (3), 10E-hymenialdisine (4), 10Z-hymenialdisine (5), hymenin (6), oroidin (7), and 4,5-dibromopyrrole-2-carbonamide (8). Both 4 and 5 showed significant enzyme inhibitory activity (IC(50) 3 and 6 nM, respectively). Secondary assays identified these compounds as potent MEK-1 inhibitors. Compounds 4 and 5 also inhibited the growth of human tumor LoVo cells.

Products