Journal article
Synthesis and structure–activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity
Bioorganic & medicinal chemistry, Vol.14(6), pp.1771-1784
2006
DOI: 10.1016/j.bmc.2005.10.025
PMID: 16290161
Abstract
The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure–activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner–Wadsworth–Emmons coupling of one of several right-half phosphonates with the aldehyde comprising the left-half of 3-deoxyschweinfurthin B. Preparation of the requisite phosphonates, and the respective stilbenes, as well as the cytotoxicity profiles of these new compounds in the National Cancer Institute’s 60 cell-line anticancer screen is described. Several of these analogs displayed cytotoxicity patterns well-correlated with the natural product and differences in activity of ∼10 3 across the various cell lines. Together, these assay results indicate the importance of at least one free phenol group on the aromatic D-ring of this system for differential cytotoxicity.
Details
- Title: Subtitle
- Synthesis and structure–activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity
- Creators
- Jeffrey D Neighbors - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USAMaya S Salnikova - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USAJohn A Beutler - Molecular Targets Development Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21701, USADavid F Wiemer - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA
- Resource Type
- Journal article
- Publication Details
- Bioorganic & medicinal chemistry, Vol.14(6), pp.1771-1784
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.bmc.2005.10.025
- PMID
- 16290161
- ISSN
- 0968-0896
- eISSN
- 1464-3391
- Language
- English
- Date published
- 2006
- Academic Unit
- Neuroscience and Pharmacology; Chemistry
- Record Identifier
- 9983985860302771
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