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Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads.

Chen QH, Kingston DG - Nat Prod Rep (2014)

Bottom Line: Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents.Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines.A high-resolution crystal structure of αβ-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA. qchen@csufresno.edu.

ABSTRACT
Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines. A high-resolution crystal structure of αβ-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability. This review provides an overview of current developments of zampanolide and its related but less potent analogue dactylolide, covering their natural sources and isolation, structure and conformation, cytotoxic potential, structure-activity studies, mechanism of action, and syntheses.

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Related in: MedlinePlus

Structures of zampanolide and dactylolide.
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fig1: Structures of zampanolide and dactylolide.

Mentions: (–)-Zampanolide (1) (Fig. 1)7 is a 20-membered polyketide first isolated from a marine sponge in 1996, and is a unique and recent addition to the class of MSAs.8 It exhibits low nanomolar cytotoxicity against both drug sensitive and multi-drug resistant cancer cell lines, and induces microtubule bundle formation.8 Its potent activity combined with its low number of chiral centres makes it an attractive compound for large-scale synthetic preparation for further study or clinical applications. As described in more detail below, the unique effects of zampanolide on tubulin assembly and its superior activity compared with that of paclitaxel against several multi-drug resistant cancer cell lines suggests that this natural macrolide could exhibit a unique spectrum of cytotoxic activities in a clinical setting and could be a valuable addition to existing anticancer drugs.


Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads.

Chen QH, Kingston DG - Nat Prod Rep (2014)

Structures of zampanolide and dactylolide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126874&req=5

fig1: Structures of zampanolide and dactylolide.
Mentions: (–)-Zampanolide (1) (Fig. 1)7 is a 20-membered polyketide first isolated from a marine sponge in 1996, and is a unique and recent addition to the class of MSAs.8 It exhibits low nanomolar cytotoxicity against both drug sensitive and multi-drug resistant cancer cell lines, and induces microtubule bundle formation.8 Its potent activity combined with its low number of chiral centres makes it an attractive compound for large-scale synthetic preparation for further study or clinical applications. As described in more detail below, the unique effects of zampanolide on tubulin assembly and its superior activity compared with that of paclitaxel against several multi-drug resistant cancer cell lines suggests that this natural macrolide could exhibit a unique spectrum of cytotoxic activities in a clinical setting and could be a valuable addition to existing anticancer drugs.

Bottom Line: Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents.Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines.A high-resolution crystal structure of αβ-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA. qchen@csufresno.edu.

ABSTRACT
Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines. A high-resolution crystal structure of αβ-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability. This review provides an overview of current developments of zampanolide and its related but less potent analogue dactylolide, covering their natural sources and isolation, structure and conformation, cytotoxic potential, structure-activity studies, mechanism of action, and syntheses.

Show MeSH
Related in: MedlinePlus