Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region

Member of
HBOI Faculty Contributions
Contributors
Paterson, Ian
Gardner, Nicola M.
Guzman, Esther A.
Wright, Amy E.
Publisher
Elsevier B.V.
Date Issued
2008-12-01
Note

By exploiting a Still-Gennari olefination of a common C11-C26 aldehyde with a C4-C10 or C1-C10 β-ketophosphonate, three modified C2-C6 region analogues of the 22-membered macrolide dictyostatin were synthesised and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including the Taxol-resistant NCI/ADR-Res cell line. 6-Desmethyldictyostatin and 2,3-dihydrodictyostatin displayed potent (low nanomolar) antiproliferative activity, intermediate between dictyostatin and discodermolide, while 2,3,4,5-tetrahydrodictyostatin showed activity comparable to discodermolide. As with dictyostatin, these simplified analogues act through a mechanism of microtubule stabilisation, G2/M arrest and apoptosis.

Language
English
Type
Text
Genre
article
Extent
6 p.
Subject (Topical)
Bioorganic chemistry
Cancer--Research
Identifier
1591053
Additional Information
By exploiting a Still-Gennari olefination of a common C11-C26 aldehyde with a C4-C10 or C1-C10 β-ketophosphonate, three modified C2-C6 region analogues of the 22-membered macrolide dictyostatin were synthesised and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including the Taxol-resistant NCI/ADR-Res cell line. 6-Desmethyldictyostatin and 2,3-dihydrodictyostatin displayed potent (low nanomolar) antiproliferative activity, intermediate between dictyostatin and discodermolide, while 2,3,4,5-tetrahydrodictyostatin showed activity comparable to discodermolide. As with dictyostatin, these simplified analogues act through a mechanism of microtubule stabilisation, G2/M arrest and apoptosis.
This manuscript is a version of an article published by Elsevier www.elsevier.com/locate/bmcl and may be cited as Paterson, Ian, Nicola M. Gardner, Esther Guzman, Amy E. Wright. (2008). Total synthesis and biological evaluation of potent analogues of dictyostatin: Modification of the C2-C6 dienoate region. Bioorganic & Medicinal Chemistry Letters, 18(23)6268‐6272 doi:10.1016/j.bmcl.2008.09.109 and is available at www.sciencedirect.com
Florida Atlantic University. Harbor Branch Oceanographic Institute contribution #1734.
Date Backup
2008-12-01
Date Text
2008-12-01
DOI
10.1016/j.bmcl.2008.09.109
Date Issued (EDTF)
2008-12-01
Extension


FAU
FAU
admin_unit="FAU01", ingest_id="ing5412", creator="creator:SPATEL", creation_date="2010-03-26 14:02:15", modified_by="super:FAUDIG", modification_date="2014-02-10 08:19:54"

IID
FADT1591053
Issuance
single unit
Person Preferred Name

Paterson, Ian

creator

Physical Description

pdf
6 p.
PURL
http://purl.flvc.org/FCLA/DT/1591053
Title Plain
Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region
URL
http://purl.flvc.org/FCLA/DT/1591053
Origin Information

Elsevier B.V.
2008-12-01
single unit
Title
Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region
Other Title Info

Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region