Synthesis and cancer cell cytotoxicity of substituted xanthenes.
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.
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Rajan
R
Giri
John R
JR
Goodell
Chenguo
C
Xing
Adam
A
Benoit
Harneet
H
Kaur
Hiroshi
H
Hiasa
David M
DM
Ferguson
D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization; D014966:Xanthenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D014966:Xanthenes