Synthesis and Evaluation of Cytotoxicity and Antioxidant Properties of Polyfluorinated Phosphorus-containing 1,4-Benzoquinones and 1,4-Naphthoquinones
O. D. Zakharova
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 8 Lavrentiev Ave., 630090 Novosibirsk, Russia
L. P. Ovchinnikova
Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, 10 Lavrentiev Ave., 630090 Novosibirsk, Russia
S. I. Zhivetyeva
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of Russian Academy of Sciences, 9 Lavrentiev Ave., 630090 Novosibirsk, Russia
L. I. Goryunov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of Russian Academy of Sciences, 9 Lavrentiev Ave., 630090 Novosibirsk, Russia
V. D. Shteingarts
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of Russian Academy of Sciences, 9 Lavrentiev Ave., 630090 Novosibirsk, Russia
E. V. Tretyakov *
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of Russian Academy of Sciences, 9 Lavrentiev Ave., 630090 Novosibirsk, Russia
G. A. Nevinsky
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 8 Lavrentiev Ave., 630090 Novosibirsk, Russia
*Author to whom correspondence should be addressed.
Abstract
Aim: Synthesis and analysis of antioxidant and antitumor properties of fluorinated phosphorus-containing derivatives of tetrafluoro-1,4-benzoquinone and hexafluoro-1,4-naphthoquinone.
Methodology: All compounds were synthesized by amino- and phosphanodefluorination with corresponding amines and phosphanes. The cytotoxicity of these fluorinated benzoquinones and naphthoquinones was compared using human myeloma and human mammary adenocarcinoma as target tumors, as well as normal mouse fibroblasts cells. Their mutagenic and antioxidant properties in a Salmonella tester strain were also evaluated.
Results: All the benzoquinones suppressed the growth of the two lines of tumor cells at approximately 3.2–90-fold higher concentrations than the naphthoquinones. In addition, the naphthoquinones were universal, while the benzoquinones were selective toward suppression of different tumor cells. At the same time, the benzoquinones and naphthoquinones demonstrated similar antioxidant properties, and protected bacterial cells against spontaneous and H2O2-dependent mutagenesis at comparable concentrations.
Conclusion: All compounds are effective antioxidants and suppress the growth of tumor cells.
Keywords: Polyfluorinated phosphorus-containing 1,4-benzoquinones and 1,4-naphthoquinones, nucleophilic substitution, antioxidant properties, cytotoxicity