Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds

J Am Chem Soc. 2013 Jul 10;135(27):10164-71. doi: 10.1021/ja404578u. Epub 2013 Jun 26.


Microtubules continue to be one of the most successful anticancer drug targets and a favorite hit for many naturally occurring molecules. While two of the most successful representative agents in clinical use, the taxanes and the vinca alkaloids, come from terrestrial sources, the sea has also proven to be a rich source of new tubulin-binding molecules. We describe herein the first isolation, structural elucidation and total synthesis of two totally new polyketides isolated from the Madagascan sponge Lithoplocamia lithistoides . Both PM050489 and PM060184 show antimitotic properties in human tumor cells lines at subnanomolar concentrations and display a distinct inhibition mechanism on microtubules. The development of an efficient synthetic procedure has solved the supply problem and, following pharmaceutical development, has allowed PM060184 to start clinical studies as a promising new drug for cancer treatment.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HT29 Cells
  • Humans
  • Molecular Conformation
  • Polyketides / chemical synthesis
  • Polyketides / isolation & purification
  • Polyketides / pharmacology*
  • Porifera / chemistry*
  • Pyrones / chemical synthesis
  • Pyrones / isolation & purification
  • Pyrones / pharmacology*
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • PM050489
  • Polyketides
  • Pyrones
  • plocabulin