1286745-05-8Relevant academic research and scientific papers
Phosphonium betaines derived from hexafluoro-1,4-naphthoquinone: Synthesis and cytotoxic and antioxidant activities
Zhivetyeva, Svetlana I.,Zakharova, Olga D.,Ovchinnikova, Ludmila P.,Baev, Dmitry S.,Bagryanskaya, Irina Yu.,Shteingarts, Vitalij D.,Tolstikova, Tatiana G.,Nevinsky, Georgy A.,Tretyakov, Evgeny V.
, p. 68 - 77 (2016)
Fluorinated derivatives of 1,4-naphthoquinones are highly potent inhibitors of Cdc25A and Cdc25B phosphatases; they suppress the growth of tumor cells. Four derivatives of phosphonium betaines derived from hexafluoro-1,4-naphthoquinone: (triphenyl[5,6,7,8-tetrafluoro-1-oxido-4-oxo-3-(phenylimino)-3,4-dihydronaphthalen-2-yl]phosphonium) (4), ((3,5-difluorophenyl)(methyl)phenyl(5,6,7,8-tetrafluoro-3-oxido-1,4-dioxo-1,4-dihydronaphthalen-2-yl)phosphonium) (5), ((2,5-difluorophenyl)(methyl)phenyl(5,6,7,8-tetrafluoro-3-oxido-1,4-dioxo-1,4-dihydronaphthalen-2-yl)phosphonium) (6) and ((3,5-difluorophenyl)diphenyl(5,6,7,8-tetrafluoro-3-oxido-1,4-dioxo-1,4-dihydronaphthalen-2-yl)phosphonium) (7) were synthesized for the first time. Their cytotoxicity toward human mammary adenocarcinoma, human myeloma, hamster and murine and fibroblasts as well as their antioxidant and mutagenic effects on a Salmonella tester strain were analyzed. All four substances showed comparable IC50values in terms of suppression of tumor cell growth, which were from two- to ninefold lower comparing with those of fibroblasts. To identify the features of spatial orientation and noncovalent interactions of the new phosphonium betaines in the binding site of Cdc25B, a molecular docking analysis was carried out. It showed that the interactions of the analyzed compounds with a Cdc25B model binding site are characterized by the presence of a large number of acceptors (fluorine and oxygen atoms, forming halogen and hydrogen bonds) and by participation of pi-systems and phosphorus in specific electrostatic interactions that may result in inhibition of enzymes of the Cdc25 family. In addition, compounds 5 and 6 (especially the latter) were found to be effective antioxidants protecting bacterial cells from H2O2-induced and spontaneous and mutagenesis at significantly lower concentrations (IC50?=?0.09 to 1.8?μM) than those of derivatives 4 and 7 (86–92?μM). Taking into account these data (together with the good cytotoxic effect on cancer cells comparing with normal mammalian cells) we can propose compounds 5 and 6 as possible useful inhibitors of tumor cell growth and antioxidants.
Synthesis of diphenyl(X)phosphonium betaines (X = CH3, C 6H5, 2,5-F2C6H3) from hexafluoro-1,4-naphthoquinone
Goryunov, Leonid I.,Zhivetyeva, Svetlana I.,Nevinsky, Georgy A.,Shteingartsa, Vitalij D.
experimental part, p. 185 - 191 (2011/06/22)
Betaines 5,6,7,8-tetrafluoro-3-(triphenyl-λ5- phosphanylidene)-1,2,3,4-tetrahydronaphthalene-1,2,4-trione, 5,6,7,8-tetrafluoro-3-(methyldiphenyl-λ5-phosphanylidene)-1,2, 3,4-tetrahydronaphthalene-1,2,4-trione, and 3-[(2,5-difluorophenyl)diphenyl- λ5-phosphanylidene]-5,6,7,8-tetrafluoro-1,2,3, 4-tetrahydronaphthalene-1,2, 4-trione have been synthesized via fluorine substitution in the quinone ring of hexafluoro-1,4-naphthoquinone by tertiary phosphines RPh2? (R = , Ph, 2,5-F2C6H 3) and methanol in 90, 30 and 62% yields, respectively. The first naphthalenetrione formed also upon interaction of pentafluoro-1,4-naphthoquinone with triphenylphosphine in methanol. The new 1,4-dibenzodioxine derivative - 6,11-difluoro-9-(triphenyl-λ5-phosphanylidene)-7,8,9, 10-tetrahydro-5,12-dioxatetracene-7,8,10-trione - has been obtained in a 83% yield by fluorine substitution in the benzene moiety of a naphthoquinone skeleton of this betaine by the action of pyrocatechol at the presence of potassium carbonate in DMSO. ARKAT-USA, Inc.
