C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro
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 c...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2018-03-01
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| Series: | Nanoscale Research Letters |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s11671-018-2490-9 |
| _version_ | 1797708005207179264 |
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| author | A. Grebinyk S. Prylutska I. Grynyuk B. Kolp V. Hurmach T. Sliva V. Amirkhanov V. Trush O. Matyshevska M. Slobodyanik Yu. Prylutskyy M. Frohme U. Ritter |
| author_facet | A. Grebinyk S. Prylutska I. Grynyuk B. Kolp V. Hurmach T. Sliva V. Amirkhanov V. Trush O. Matyshevska M. Slobodyanik Yu. Prylutskyy M. Frohme U. Ritter |
| author_sort | A. Grebinyk |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T06:15:58Z |
| format | Article |
| id | doaj.art-998639c7606d4713a6dea07b04974eb2 |
| institution | Directory Open Access Journal |
| issn | 1931-7573 1556-276X |
| language | English |
| last_indexed | 2024-03-12T06:15:58Z |
| publishDate | 2018-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Nanoscale Research Letters |
| spelling | doaj.art-998639c7606d4713a6dea07b04974eb22023-09-03T02:39:23ZengSpringerOpenNanoscale Research Letters1931-75731556-276X2018-03-011311910.1186/s11671-018-2490-9C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In VitroA. Grebinyk0S. Prylutska1I. Grynyuk2B. Kolp3V. Hurmach4T. Sliva5V. Amirkhanov6V. Trush7O. Matyshevska8M. Slobodyanik9Yu. Prylutskyy10M. Frohme11U. Ritter12Taras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”Taras Shevchenko National University of Kyiv, Faculty of ChemistryTaras Shevchenko National University of Kyiv, Faculty of ChemistryTechnical University of Applied Sciences WildauTaras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”Taras Shevchenko National University of Kyiv, Faculty of ChemistryTaras Shevchenko National University of Kyiv, Faculty of ChemistryTaras Shevchenko National University of Kyiv, Faculty of ChemistryTaras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”Taras Shevchenko National University of Kyiv, Faculty of ChemistryTaras Shevchenko National University of Kyiv, ESC “Institute of Biology and Medicine”Technical University of Applied Sciences WildauTechnical University IlmenauAbstract 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.http://link.springer.com/article/10.1186/s11671-018-2490-9Diphenyl-N-(trichloroacetyl)-amidophosphate (HL)C60 fullereneLeukemic CCRF-CEM cellsDNAMolecular simulation |
| spellingShingle | A. Grebinyk S. Prylutska I. Grynyuk B. Kolp V. Hurmach T. Sliva V. Amirkhanov V. Trush O. Matyshevska M. Slobodyanik Yu. Prylutskyy M. Frohme U. Ritter C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro Nanoscale Research Letters Diphenyl-N-(trichloroacetyl)-amidophosphate (HL) C60 fullerene Leukemic CCRF-CEM cells DNA Molecular simulation |
| 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 |
| title_full | C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro |
| title_fullStr | C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro |
| title_full_unstemmed | C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro |
| title_short | C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro |
| title_sort | c60 fullerene effects on diphenyl n trichloroacetyl amidophosphate interaction with dna in silico and its cytotoxic activity against human leukemic cell line in vitro |
| topic | Diphenyl-N-(trichloroacetyl)-amidophosphate (HL) C60 fullerene Leukemic CCRF-CEM cells DNA Molecular simulation |
| url | http://link.springer.com/article/10.1186/s11671-018-2490-9 |
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