Synthesis and cancer cell cytotoxicity of substituted xanthenes

Rajan Giri, John R. Goodell, Chenguo Xing, Adam Benoit, Harneet Kaur, Hiroshi Hiasa, David M. Ferguson

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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 languageEnglish (US)
Pages (from-to)1456-1463
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number4
DOIs
StatePublished - Feb 15 2010

Keywords

  • Cancer cells
  • Cytotoxicity
  • DNA binding
  • DU-145
  • Drug design
  • HeLa
  • Intercalation
  • MCF-7
  • Molecular modeling
  • SAR
  • Topoisomerase
  • Xanthene
  • Xanthone

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