Ukr.Biochem.J. 2020; Volume 92, Issue 4, Jul-Aug, pp. 55-62


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

N. S. Finiuk1,2, I. I. Ivasechko1, O. Yu. Klyuchivska1,
H. M. Kuznietsova3, V. K. Rybalchenko3, R. S. Stoika1,2,3*

1Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
2Ivan Franko National University of Lviv, Ukraine;
3Taras Shevchenko National University of Kyiv, Ukraine;

Received: 21 November 2019; Accepted: 15 May 2020

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.

Keywords: , ,


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