Cytotoxicity of new alkylamino- and phenylamino-containing polyfluorinated derivatives of 1,4-naphthoquinone

Cytotoxicity of new alkylamino- and phenylamino-containing polyfluorinated derivatives of 1,4-naphthoquinone Full article

Journal

European Journal of Medicinal Chemistry
ISSN: 0223-5234 , E-ISSN: 1768-3254

Output data

Year: 2010, Volume: 45, Number: 6, Pages: 2321-2326 Pages count : DOI: 10.1016/j.ejmech.2010.02.009

Tags

Fluorinated derivatives of 1,4-naphthoquinones; Antitumor

Authors

Zakharova Ol'ga D. ¹ , Ovchinnikova Ludmila P. ² , Goryunov Leonid I. ³ , Troshkova Nadezhda M. ³ , Shteingarts Vitalij D. ³ , Nevinsky Georgy A. ^1,2

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Div, Inst Biol Chem & Fundamental Med, Novosibirsk 630090, Russia
2	(Данные Web of science) Russian Acad Sci, Siberian Div, Inst Cytol & Genet, Novosibirsk 630090, Russia
3	(Данные Web of science) Russian Acad Sci, Siberian Div, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk 630090, Russia

Fluorinated derivatives of 1,4-naphthoquinone are highly potent inhibitors of Cdc25A and Cdc25 phosphatases and growth of tumor cells. Five new N-substituted polyfluorinated derivatives of 2-amino-1,4-naphthoquinone were synthesized and their mutagenic and antioxidant properties in Salmonella cells, as well as cytotoxicity in human myeloma (RPMI 8226), human mammary adenocarcinoma (MCF-7), mouse fibroblasts (LMTK) and primary mouse fibroblast cells (PMF) were studied 2-tert-Butylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (1) inhibited the growth of normal control and tumor cells at the same concentration. Three compounds: 2-diethylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (2), 2-ethylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (3), 2-phenylamino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (4) exhibited a 50% decrease in the growth of cancer cells at low and comparable concentrations (2 4-8 6 mu M) while being remarkably less cytotoxic toward normal LMTK and PMF cells. Quinones (1)-(4), but not 2-phenylamino-3-methyl-5,6,7,8-tetrafluoro-1,4-naphthoquinone (5), efficiently suppressed spontaneous mutagenesis in Salmonella cells, while all compounds 1-5 decreased the mutagenic effect of H2O2 on bacterial cells. Their possible perspectives as anticancer drugs are shortly discussed.

Zakharova O.D. , Ovchinnikova L.P. , Goryunov L.I. , Troshkova N.M. , Shteingarts V.D. , Nevinsky G.A.
Cytotoxicity of new alkylamino- and phenylamino-containing polyfluorinated derivatives of 1,4-naphthoquinone
European Journal of Medicinal Chemistry. 2010. V.45. N6. P.2321-2326. DOI: 10.1016/j.ejmech.2010.02.009 WOS Scopus РИНЦ

Published print:

Jun 1, 2010

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