@article{GrebinykPrylutskaGrynyuketal.2018, author = {Grebinyk, Anna and Prylutska, Svitlana and Grynyuk, I. and Kolp, Benjamin and Hurmach, V. and Sliva, T. and Amirkhanov, V. and Trush, V. and Matyshevska, Olga and Slobodyanik, M. and Prylutskyy, Yuriy and Frohme, Marcus and Ritter, Uwe}, title = {C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro}, series = {Nanoscale Research Letters}, volume = {2018}, journal = {Nanoscale Research Letters}, issn = {1556-276X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10515}, pages = {1 -- 9}, year = {2018}, abstract = {New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C60 fullerene. According to molecular simulation results, C60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl3 group by ion-π bonds with C60 molecule and by electrostatic bonds with DNA G nucleotide. With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C60 fullerene and HL, the value of IC50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CЕM cells proliferation. Application of C60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.}, language = {en} } @article{PrylutskaGrynyukGrebinyketal.2017, author = {Prylutska, Svitlana and Grynyuk, I. and Grebinyk, Anna and Hurmach, V. and Shatrava, Iu. and Sliva, T. and Amirkhanov, V. and Prylutskyy, Yuriy and Matyshevska, Olga and Slobodyanik, M. and Frohme, Marcus and Ritter, Uwe}, title = {Cytotoxic Effects of Dimorfolido-N-Trichloroacetylphosphorylamide and Dimorfolido-N-Benzoylphosphorylamide in Combination with C60 Fullerene on Leukemic Cells and Docking Study of Their Interaction with DNA}, series = {Nanoscale Research Letters}, volume = {12}, journal = {Nanoscale Research Letters}, number = {124}, issn = {1556-276X}, doi = {10.1186/s11671-017-1893-3}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9273}, year = {2017}, abstract = {Dimorfolido-N-trichloroacetylphosphorylamide (HL1) and dimorfolido-N-benzoylphosphorylamide (HL2) as representatives of carbacylamidophosphates were synthesized and identified by the methods of IR, 1H, and 31P NMR spectroscopy. In vitro HL1 and HL2 at 1 mM concentration caused cell specific and time-dependent decrease of leukemic cell viability. Compounds caused the similar gradual decrease of Jurkat cells viability at 72 h (by 35\%). HL1 had earlier and more profound toxic effect as compared to HL2 regardless on leukemic cell line. Viability of Molt-16 and CCRF-CEM cells under the action of HL1 was decreased at 24 h (by 32 and 45\%, respectively) with no substantial further reducing up to 72 h. Toxic effect of HL2 was detected only at 72 h of incubation of Jurkat and Molt-16 cells (cell viability was decreased by 40 and 45\%, respectively). It was shown that C60 fullerene enhanced the toxic effect of HL2 on leukemic cells. Viability of Jurkat and CCRF-CEM cells at combined action of C60 fullerene and HL2 was decreased at 72 h (by 20 and 24\%, respectively) in comparison with the effect of HL2 taken separately. In silico study showed that HL1 and HL2 can interact with DNA and form complexes with DNA both separately and in combination with C60 fullerene. More stable complexes are formed when DNA interacts with HL1 or C60 + HL2 structure. Strong stacking interactions can be formed between HL2 and C60 fullerene. Differences in the types of identified bonds and ways of binding can determine distinction in cytotoxic effects of studied compounds.}, language = {en} }