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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

Loh's synthesis of fragment C9–C17 of zampanolide.
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sch42: Loh's synthesis of fragment C9–C17 of zampanolide.

Mentions: As shown in Scheme 42, Loh and co-workers reported a diastereoselective construction of fragment C9–C17 of zampanolide via In(OTf)3-catalyzed intramolecular 2,5-oxonium-ene cyclization from enal 25.84 In(OTf)3-catalyzed intramolecular 2,5-oxonium-ene cyclization of 198 and aldehyde 22, followed by desilylation with TBAF, provided the desired cyclization product 199 with good syn diastereoselectivity (75 : 25) as two inseparable isomers. The observed predominant 2,6-syn selectivity can be rationalized by the cyclic six-membered chair-like transition state favouring an all-equatorial substitution pattern.


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

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

Loh's synthesis of fragment C9–C17 of zampanolide.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

sch42: Loh's synthesis of fragment C9–C17 of zampanolide.
Mentions: As shown in Scheme 42, Loh and co-workers reported a diastereoselective construction of fragment C9–C17 of zampanolide via In(OTf)3-catalyzed intramolecular 2,5-oxonium-ene cyclization from enal 25.84 In(OTf)3-catalyzed intramolecular 2,5-oxonium-ene cyclization of 198 and aldehyde 22, followed by desilylation with TBAF, provided the desired cyclization product 199 with good syn diastereoselectivity (75 : 25) as two inseparable isomers. The observed predominant 2,6-syn selectivity can be rationalized by the cyclic six-membered chair-like transition state favouring an all-equatorial substitution pattern.

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