Microtubule-stabilizing activity of zampanolide, a potent macrolide isolated from the Tongan marine sponge Cacospongia mycofijiensis

J Med Chem. 2009 Nov 26;52(22):7328-32. doi: 10.1021/jm901249g.

Abstract

Zampanolide (1), a 20-membered macrolide from a Tongan marine sponge, stabilizes microtubules and blocks cells in G(2)/M of the cell cycle. Zampanolide is cytotoxic in the low nanomolar range and induces microtubule bundles in cells. It leads to tubulin assembly in cells and in purified tubulin preparations and is not a substrate for the P-glycoprotein drug efflux pump. Zampanolide, with only four stereogenic centers, may be amenable to large-scale synthetic preparation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Cell Cycle / drug effects
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Macrolides / chemistry
  • Macrolides / isolation & purification*
  • Macrolides / pharmacology*
  • Microtubules / drug effects*
  • Microtubules / metabolism*
  • Porifera / chemistry*
  • Protein Multimerization / drug effects
  • Protein Structure, Quaternary
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tubulin / metabolism

Substances

  • Antineoplastic Agents
  • Macrolides
  • Tubulin
  • zampanolide