Journal article
Fluorescent schweinfurthin B and F analogs with anti-proliferative activity
Bioorganic & medicinal chemistry, Vol.18(18), pp.6734-6741
09/15/2010
DOI: 10.1016/j.bmc.2010.07.056
PMCID: PMC3967504
PMID: 20724169
Abstract
The synthesis of several new fluorescent analogs of schweinfurthins B and F is described, along with assays that demonstrates that these compounds retain potent and differential activities against select human cancer cell lines. Use of fluorescence microscopy shows differences between the localization of the active and relatively inactive schweinfurthin analogs. The natural tetracyclic schweinfurthins are potent and selective inhibitors of cell growth in the National Cancer Institute’s 60 cell-line screen. At this time, the mechanism or cellular target that underlies this activity has not yet been identified, and efforts to illuminate the schweinfurthins’ mode of action would benefit from development of potent fluorescent analogs that could be readily visualized within cells. This report describes the synthesis of fluorescent analogs of schweinfurthins B and F, and demonstrates that these compounds retain the potent and differentially toxic activities against select human cancer cells that are characteristic of the natural schweinfurthins. In addition, the synthesis of control compounds that maintain parallel fluorescent properties, but lack the potent activity of the natural schweinfurthin is described. Use of fluorescence microscopy shows differences between the localization of the active and relatively inactive schweinfurthin analogs. The active compounds localize in peripheral puncta which may identify the site(s) of activity.
Details
- Title: Subtitle
- Fluorescent schweinfurthin B and F analogs with anti-proliferative activity
- Creators
- Joseph J Topczewski - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USACraig H Kuder - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1294, USAJeffrey D Neighbors - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USARaymond J Hohl - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1294, 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.18(18), pp.6734-6741
- DOI
- 10.1016/j.bmc.2010.07.056
- PMID
- 20724169
- PMCID
- PMC3967504
- NLM abbreviation
- Bioorg Med Chem
- ISSN
- 0968-0896
- eISSN
- 1464-3391
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust; DOI: 10.13039/100000054, name: the National Cancer Institute, award: R41CA126020
- Language
- English
- Date published
- 09/15/2010
- Academic Unit
- Neuroscience and Pharmacology; Chemistry; Internal Medicine
- Record Identifier
- 9983985704902771
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