Fluorescent schweinfurthin B and F analogs with anti-proliferative activity.

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. Copyright (c) 2010 Elsevier Ltd. All rights reserved.