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, 9g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3-carboxamide), was found to inhibit cancer cell growth with IC50 values ranging from 36 to 50 μM 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 9g). 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.
Original language | English (US) |
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Pages (from-to) | 1456-1463 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 18 |
Issue number | 4 |
DOIs | |
State | Published - Feb 15 2010 |
Keywords
- Cancer cells
- Cytotoxicity
- DNA binding
- DU-145
- Drug design
- HeLa
- Intercalation
- MCF-7
- Molecular modeling
- SAR
- Topoisomerase
- Xanthene
- Xanthone