L. I. Goryunov

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

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 microM) 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.

Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety

Fluorinated derivatives of 1,4-naphthoquinones are highly potent inhibitors of Cdc25A and Cdc25B phosphatases and growth of tumor cells. Eight new derivatives of polyfluoro-1,4-naphthoquinone were synthesized and their cytotoxicity in human myeloma, human mammary adenocarcinoma, mouse fibroblasts and primary mouse fibroblast cells as well as their mutagenic and antioxidant properties in a Salmonella tester strain were studied. The efficiency of suppressing the growth of two lines of tumor cells decreased in the order: 2-(2-hydroxy-ethylamino)-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (1), 2,3-dimethoxy-5,6,7,8-tetrafluoro-1,4-naphthoquinone (2), 2-[2-hydroxyethyl(methyl)amino]-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (3), 2-morpholino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (4), 2-[bis-(2-hydroxyethyl)amino]-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (5), 2-[(2-hydroxy)ethylsulfanyl)]-5,6,7,8-tetrafluoro-1,4-naphthoquinone (6), 2-methoxy-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (7), and 1,4-dioxo-3-(1-pyridinio)-1,4-dihydro-5,6,7,8-tetrafluoronaphthalene-2-olate (8). Taking into account these data together with the better cytotoxic effect against cancer cells as compared with normal mammalian cells, protecting of bacterial cells from spontaneous and H(2)O(2)-dependent mutagenesis, and lower general toxicity of the compounds towards different cells, one can propose that compounds 3-5 may be considered as useful potential inhibitors of growth of tumor cells.

Synthesis of 2,3′,4′-tricyanobiphenyl derivatives and tetraphenylphthalocyanines based thereon

The nitration of 2,3′,4′-tricyanobiphenyl with subsequent transformations of the obtained product provided 4-X-2,3′,4′-tricyanobiphenyls (X = NO2, NH2, NHCOCH3, Br, I). The condensation of the initial biphenyl or its 4-X-derivatives (X = NO2, NHCOCH3, Br, I) in the presence of zinc acetate afforded the corresponding zinc complexes of tetra(4-X-2-cyanophenyl)phthalocyanines.

Synthesis of 2-aminopentafluoro-1,4-naphthoquinone derivatives

Potential biologically active derivatives of 2-aminopentafluoro-1,4-naphthoquinone modified at the amino group were synthesized in 32–96% yield by reactions of hexafluoro-1,4-naphthoquinone with nitrogen-centered nucleophiles.

Synthesis of phthalonitriles containing ω-alkenyl, ω-(alkylsulfanyl)alkyl, and ω-(alkylsulfonyl)alkyl substituents and phthalocyanine derivatives based thereon

Alkylation of phthalonitrile radical anion sodium salt with terminal alkenyl bromides (4-bromobut-1-ene, 5-bromopent-1-ene, and 6-bromohex-1-ene) gave the corresponding 4-alkenylphthalonitriles which reacted with alkanethiols (BuSH and n-C10H21SH) to produce 4-(ω-alkylsulfanylalkyl)phthalonitriles. Oxidation of the latter with hydrogen peroxide afforded 4-(ω-alkylsulfonylalkyl)phthtalonitriles. 4-Alkenyl- and 4-(ω-alkylsulfonylalkyl)phthalonitriles were brought into condensation with zinc(II) acetate to obtain the corresponding zinc phthalocyanines.