title: Cytotoxic Effects of Dimorfolido-N-Trichloroacetylphosphorylamide and Dimorfolido-N-Benzoylphosphorylamide in Combination with C60Fullerene on Leukemic Cells and Docking Study of Their Interaction with DNA.
abstract: Dimorfolido-N-trichloroacetylphosphorylamide (HL1) and dimorfolido-N-benzoylphosphorylamide (HL2) as representatives of carbacylamidophosphates were synthesized and identified by the methods of IR,1H, and31P 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 C60fullerene enhanced the toxic effect of HL2 on leukemic cells. Viability of Jurkat and CCRF-CEM cells at combined action of C60fullerene 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 C60fullerene. More stable complexes are formed when DNA interacts with HL1 or C60+ HL2 structure. Strong stacking interactions can be formed between HL2 and C60fullerene. Differences in the types of identified bonds and ways of binding can determine distinction in cytotoxic effects of studied compounds.
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine. psvit@bigmir.net.
authors.forename: S
authors.initials: S
authors.lastname: Prylutska
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: I
authors.initials: I
authors.lastname: Grynyuk
authors.affiliation: Technical University of Applied Sciences of Wildau, 1 Hochschulring Str., Wildau, 15745, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Grebinyk
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: V
authors.initials: V
authors.lastname: Hurmach
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: Iu
authors.initials: I
authors.lastname: Shatrava
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: T
authors.initials: T
authors.lastname: Sliva
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: V
authors.initials: V
authors.lastname: Amirkhanov
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: Yu
authors.initials: Y
authors.lastname: Prylutskyy
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: O
authors.initials: O
authors.lastname: Matyshevska
authors.affiliation: Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine.
authors.forename: M
authors.initials: M
authors.lastname: Slobodyanik
authors.affiliation: Technical University of Applied Sciences of Wildau, 1 Hochschulring Str., Wildau, 15745, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Frohme
authors.affiliation: Technical University of Ilmenau, 25 Weimarer Str., Ilmenau, 98693, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Ritter
keywords: C60 fullerene; Computer modeling; DNA; Dimorfolido-N-benzoylphosphorylamide; Dimorfolido-N-trichloroacetylphosphorylamide; Leukemic cells