Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA
Development of chemical compounds capable to supress tumor progression is a perspective strategy of cancer treatment. Heterocyclic compounds possess a broad spectrum of biological activities, including anticancer one. According to the previous results of in silico modeling maleimide derivative 1-(4-...
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2020-08-01
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| Series: | The Ukrainian Biochemical Journal |
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| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2020/09/Finiuk_4_20.pdf |
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| author | N. S. Finiuk I. I. Ivasechko O. Yu. Klyuchivska H. M. Kuznietsova V. K. Rybalchenko R. S. Stoika |
| author_facet | N. S. Finiuk I. I. Ivasechko O. Yu. Klyuchivska H. M. Kuznietsova V. K. Rybalchenko R. S. Stoika |
| author_sort | N. S. Finiuk |
| collection | DOAJ |
| description | Development of chemical compounds capable to supress tumor progression is a perspective strategy of cancer treatment. Heterocyclic compounds possess a broad spectrum of biological activities, including anticancer one. According to the previous results of in silico modeling maleimide derivative 1-(4-Cl-benzil)-3-Cl-4-(CF3-phenylamino)-1Н-pyrrole-2,5-dione (MI-1) has a potential effect as an inhibitor of tyrosine protein kinases. The present study was aimed at in vitro evaluation of MI-1 cytotoxic effects toward tumor cells of various lines. The viability of tumor cells after incubation with MI-1 was measured by means of 3,4,5-dymetyltiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) test. The MI-1 compound was shown to be toxic for a majority of studied tumor cell lines with IC50 value ranging from 0.8 to 62.2 μg/ml depending on the tissue origin of cells. The most prominent effect of MI-1 towards human cervix carcinoma (KB3-1 and KBC-1) cells with six times higher toxicity towards the multidrug resistant sub-line KBC-1 cells comparing with the action of Doxorubicin was demonstrated. MI-1 inhibited the viability of human pancreatic, hepatocarcinoma, and colon carcinoma cells only in high doses, while human and rat glioblastoma cells were not sensitive to MI-1. Thus, the MI-1 anticancer activity dropped in the following rank of tumor cells: cervix > breast > pancreatic carcinoma > liver carcinoma > colon carcinoma > glioblastoma. Experiments on replacement of methyl green dye from DNA-methyl green complex showed that MI-1 intercalated into DNA molecule structure. The increase of the amount of the additional band of super-spiral DNA in the presence of MI-1 was revealed by means of DNA retardation at electrophoresis in the agarose gel and this effect was more pronounced than the effect of doxorubicin. The data presented indicate a new DNA-targeting mechanism of maleimide derivative 1-(4-Cl-benzil)-3-Cl-4-(CF3-phenylamino)-1Н-pyrrole-2,5-dione anticancer action. |
| first_indexed | 2024-03-09T08:44:43Z |
| format | Article |
| id | doaj.art-3b3160873d374497b540a908e21cd4e2 |
| institution | Directory Open Access Journal |
| issn | 2409-4943 2413-5003 |
| language | English |
| last_indexed | 2024-03-09T08:44:43Z |
| publishDate | 2020-08-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj.art-3b3160873d374497b540a908e21cd4e22023-12-02T15:44:20ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032020-08-01924556210.15407/ubj92.04.055Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNAN. S. Finiuk0https://orcid.org/0000-0002-4112-8815I. I. Ivasechko1https://orcid.org/0000-0003-2789-0763O. Yu. Klyuchivska2https://orcid.org/0000-0001-8657-5945H. M. Kuznietsova3https://orcid.org/0000-0002-1296-1007V. K. Rybalchenko4https://orcid.org/0000-0001-5069-2621R. S. Stoika5https://orcid.org/0000-0001-5719-2187Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv; Ivan Franko National University of Lviv, UkraineInstitute of Cell Biology, National Academy of Sciences of Ukraine, LvivInstitute of Cell Biology, National Academy of Sciences of Ukraine, LvivTaras Shevchenko National University of Kyiv, UkraineTaras Shevchenko National University of Kyiv, UkraineInstitute of Cell Biology, National Academy of Sciences of Ukraine, Lviv; Ivan Franko National University of Lviv, UkraineDevelopment of chemical compounds capable to supress tumor progression is a perspective strategy of cancer treatment. Heterocyclic compounds possess a broad spectrum of biological activities, including anticancer one. According to the previous results of in silico modeling maleimide derivative 1-(4-Cl-benzil)-3-Cl-4-(CF3-phenylamino)-1Н-pyrrole-2,5-dione (MI-1) has a potential effect as an inhibitor of tyrosine protein kinases. The present study was aimed at in vitro evaluation of MI-1 cytotoxic effects toward tumor cells of various lines. The viability of tumor cells after incubation with MI-1 was measured by means of 3,4,5-dymetyltiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) test. The MI-1 compound was shown to be toxic for a majority of studied tumor cell lines with IC50 value ranging from 0.8 to 62.2 μg/ml depending on the tissue origin of cells. The most prominent effect of MI-1 towards human cervix carcinoma (KB3-1 and KBC-1) cells with six times higher toxicity towards the multidrug resistant sub-line KBC-1 cells comparing with the action of Doxorubicin was demonstrated. MI-1 inhibited the viability of human pancreatic, hepatocarcinoma, and colon carcinoma cells only in high doses, while human and rat glioblastoma cells were not sensitive to MI-1. Thus, the MI-1 anticancer activity dropped in the following rank of tumor cells: cervix > breast > pancreatic carcinoma > liver carcinoma > colon carcinoma > glioblastoma. Experiments on replacement of methyl green dye from DNA-methyl green complex showed that MI-1 intercalated into DNA molecule structure. The increase of the amount of the additional band of super-spiral DNA in the presence of MI-1 was revealed by means of DNA retardation at electrophoresis in the agarose gel and this effect was more pronounced than the effect of doxorubicin. The data presented indicate a new DNA-targeting mechanism of maleimide derivative 1-(4-Cl-benzil)-3-Cl-4-(CF3-phenylamino)-1Н-pyrrole-2,5-dione anticancer action.http://ukrbiochemjournal.org/wp-content/uploads/2020/09/Finiuk_4_20.pdf1-(4-cl-benzil)-3-cl-4-(cf3-phenylamino)-1н-pyrrole-2.5-dioneanticancer activityмтт |
| spellingShingle | N. S. Finiuk I. I. Ivasechko O. Yu. Klyuchivska H. M. Kuznietsova V. K. Rybalchenko R. S. Stoika Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA The Ukrainian Biochemical Journal 1-(4-cl-benzil)-3-cl-4-(cf3-phenylamino)-1н-pyrrole-2.5-dione anticancer activity мтт |
| title | Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA |
| title_full | Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA |
| title_fullStr | Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA |
| title_full_unstemmed | Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA |
| title_short | Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA |
| title_sort | cytotoxic action of maleimide derivative 1 4 cl benzyl 3 chloro 4 cf 3 phenylamino 1h pyrrole 2 5 dione toward mammalian tumor cells and its capability to interact with dna |
| topic | 1-(4-cl-benzil)-3-cl-4-(cf3-phenylamino)-1н-pyrrole-2.5-dione anticancer activity мтт |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2020/09/Finiuk_4_20.pdf |
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