Synthesis and cancer cell cytotoxicity of substituted xanthenes.

Abstract

A series of substituted xanthenes was synthesized and screened for activity using DU-145, MCF-7, and HeLa cancer cell growth inhibition assays. The most potent compound, 9 g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3-carboxamide), was found to inhibit cancer cell growth with IC(50) values ranging from 36 to 50 microM across all three cancer cell lines. Structure-activity relationship (SAR) data is presented that indicates additional gains in potency may be realized through further derivatization of the compounds (e.g., the incorporation of a 7-fluoro substituent to 9 g). Results are also presented that suggest the compounds function through a unique mechanism of action as compared to that of related acridine and xanthone anticancer agents (which have been shown to intercalate into DNA and inhibit topoisomerase II activity). A structural comparison of these compounds suggests the differences in function may be due to the structure of the xanthene heterocycle which adopts a nonplanar conformation about the pyran ring.

• Authors: Rajan Giri, John R Goodell, Chenguo Xing, Adam Benoit, Harneet Kaur, Hiroshi Hiasa, David M Ferguson
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 18 Issue 4 Pg. 1456-63 (Feb 15 2010) ISSN: 1464-3391 [Electronic] England
• PMID: 20129790 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Xanthenes

Topics

• Drug Screening Assays, Antitumor
• HeLa Cells
• Humans
• Magnetic Resonance Spectroscopy
• Models, Molecular
• Spectrometry, Mass, Electrospray Ionization
• Xanthenes (chemical synthesis, chemistry, pharmacology)