Cytostatic, cytotoxic, and an tioxidant effects of an antitumor compound — maleimide derivative

Kuznetsova, GM
Linchak, OV
Belinskaya, IV
Chereshchuk, IO
1Milokhov, DS
1Khilya, OV
1Rybalchenko, VK
1ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv
Dopov. Nac. akad. nauk Ukr. 2019, 10:89-96
https://doi.org/10.15407/dopovidi2019.10.089
Section: Biology
Language: Ukrainian
Abstract: 

Low-molecular-weight inhibitors of protein kinases are promising as antitumor agents due to their high efficiency and relatively low toxicity. However, the number of approved chemicals is not enough for needs of modern medicine. Maleimide derivative chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1Hpyrrole- 2,5-dione (MI-1) is an inhibitor of a number of receptor and non-receptor tyrosine protein kinases. We have demonstrated that MI-1 causes apoptosis of transformed MG-63 (osteosarcoma) and SK-OV-3 (ovarian adenocarcinoma) cells, but virtually doesn’t affect the viability of normal AOB (alveolar osteoblasts) ones. Moreover, this compound inhibits the development of colorectal tumors in vivo similarly to common cytostatic 5-fluorouracil did. MI-1 mitigated manifestations and outcomes of the oxidative stress in organism and contributed to the normalization of redox balance impaired through carcinogenesis as well. That might be one of the mechanisms of realization of MI-1 antitumor activity. The compound also diminishes cancer-induced monocytosis and thrombocytosis and restores the values of liver function biochemical parameters with no impact on those of healthy animals. Hence, MI-1 has a perspective as a basis for the antitumor drugs development.

Keywords: maleimide, protein kinases
References: 

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