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.
Highlights
Nowadays, it is important to create new biocompatible nanomaterials that exhibit pharmacological properties, antitumor activity, and modulate the biological effects of chemotherapeutic drugs.Carbacylamidophosphates as the structural analog of β-diketones, that are promising class of biologically active compounds with antimitotic and antiproliferative activities, can be used as antitumor agents [1,2,3].In previous study with the use of in silico analysis, we have shown that dimethyl-N-(benzoyl)amidophosphate as representative of carbacylamidophosphates possesses an antitumor activity and interacts with Deoxyribonucleic acid (DNA) [4, 5].In vitro toxic effects of 2.5 mM dimethyl-N-(benzoyl)amidophosphate on leukemic L1210 cells were demonstrated
In previous study with the use of in silico analysis, we have shown that dimethyl-N-(benzoyl)amidophosphate as representative of carbacylamidophosphates possesses an antitumor activity and interacts with DNA [4, 5]
It was shown that toxic effects of dimethyl-N-(benzoyl)amidophosphate on leukemic cells could be facilitated by C60 fullerene [5]
Summary
It is important to create new biocompatible nanomaterials that exhibit pharmacological properties, antitumor activity, and modulate the biological effects of chemotherapeutic drugs.Carbacylamidophosphates as the structural analog of β-diketones, that are promising class of biologically active compounds with antimitotic and antiproliferative activities, can be used as antitumor agents [1,2,3].In previous study with the use of in silico analysis, we have shown that dimethyl-N-(benzoyl)amidophosphate as representative of carbacylamidophosphates possesses an antitumor activity and interacts with DNA [4, 5].In vitro toxic effects (decrease of cell viability and increase of ROS production) of 2.5 mM dimethyl-N-(benzoyl)amidophosphate on leukemic L1210 cells were demonstrated. It is important to create new biocompatible nanomaterials that exhibit pharmacological properties, antitumor activity, and modulate the biological effects of chemotherapeutic drugs. In previous study with the use of in silico analysis, we have shown that dimethyl-N-(benzoyl)amidophosphate as representative of carbacylamidophosphates possesses an antitumor activity and interacts with DNA [4, 5]. In vitro toxic effects (decrease of cell viability and increase of ROS production) of 2.5 mM dimethyl-N-(benzoyl)amidophosphate on leukemic L1210 cells were demonstrated. It was shown that toxic effects of dimethyl-N-(benzoyl)amidophosphate on leukemic cells could be facilitated by C60 fullerene [5]. C60 fullerene is a chemically stable carbon nanostructure, able to interact with biomolecules and penetrate through plasma membrane inside the cell [6,7,8] and, it can be used in biomedical applications [9,10,11,12,13]. C60 fullerene can form complexes with chemotherapeutic drugs such as doxorubicin, cisplatin, and paclitaxel, reducing their cytotoxic effect and enhancing the therapeutic effect [14,15,16,17,18]
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