Microtubule-stabilizing activity of zampanolide, a potent macrolide isolated from the Tongan marine sponge Cacospongia mycofijiensis.
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.
Field
Jessica J
JJ
Centre for Biodiscovery, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand.
Singh
A Jonathan
AJ
Kanakkanthara
Arun
A
Halafihi
Tu'ikolongahau
T
Northcote
Peter T
PT
Miller
John H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism*; D011161:Porifera / Q000737:chemistry*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D000970:Antineoplastic Agents; D018942:Macrolides; D014404:Tubulin; C444900:zampanolide