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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

Zampanolide analogs.
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fig2: Zampanolide analogs.

Mentions: Only a small amount of structure–activity work has been reported on zampanolide (1). So far, all the available analogues (Fig. 2) for SAR investigation have come from synthetic by-products or from work from the Altmann laboratory. As shown in Table 3, its N-acyl hemiaminal side chain plays a dramatic role in the nanomolar IC50 values against the four cell lines tested.19 Jennings' synthetic (–)-dactylolide (3) was 10- to 1000-fold less potent (GI50) than 1 against A549, HT29, and SK-Mel-28 cell lines. Interestingly, synthetic 3 is slightly more active than natural dactylolide against the SK-OV-3 cancer cell line.


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

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

Zampanolide analogs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Zampanolide analogs.
Mentions: Only a small amount of structure–activity work has been reported on zampanolide (1). So far, all the available analogues (Fig. 2) for SAR investigation have come from synthetic by-products or from work from the Altmann laboratory. As shown in Table 3, its N-acyl hemiaminal side chain plays a dramatic role in the nanomolar IC50 values against the four cell lines tested.19 Jennings' synthetic (–)-dactylolide (3) was 10- to 1000-fold less potent (GI50) than 1 against A549, HT29, and SK-Mel-28 cell lines. Interestingly, synthetic 3 is slightly more active than natural dactylolide against the SK-OV-3 cancer cell line.

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