Structural analogues of schweinfurthin F: Probing the steric, electronic, and hydrophobic properties of the D-ring substructure

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 4; pp. 1676 - 1683
• Main Authors: Ulrich, Natalie C., Kodet, John G., Mente, Nolan R., Kuder, Craig H., Beutler, John A., Hohl, Raymond J., Wiemer, David F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-02-2010; Elsevier
• Subjects: Anti-proliferative; Antineoplastic agents; Bioassay; Biological and medical sciences; Cell Division - drug effects; Cell Line, Tumor; Drug Screening Assays, Antitumor; General aspects; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Probes; Molecular Structure; Pharmacology. Drug treatments; Schweinfurthin; Spectrometry, Mass, Electrospray Ionization; Stilbene; Stilbenes - chemistry; Synthesis; Schweinfurthin; Anti-proliferative; Synthesis; Bioassay; Stilbene; Antineoplastic agent; Human; Lung; Resorcinol derivatives; Central nervous system; Cytotoxicity; Substructure; In vitro; Biological activity; Stilbene derivatives; Xanthene derivatives; Cell line; Chemical synthesis; Tumor cell; Lipophilicity; Physicochemical properties
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.12.063

Synthesis of a set of schweinfurthin analogues varied in the D-ring alkyl substituent and stilbene moiety has been accomplished, and the activity of these compounds has been measured in a two-cell line screen. The most potent analogue and a much less active compound also were tested in the NCI 60-cell line assay, and showed comparable potency in that more extensive screen.
The natural tetracyclic schweinfurthins are potent and selective inhibitors of cell growth in the National Cancer Institute’s 60-cell line screen. An interest in determination of their cellular or molecular target has inspired our efforts to prepare both the natural products and analogues. In this paper, chemical synthesis of analogues modified in different olefinic positions, and preliminary results from studies of their biological activity, are reported.