Application of 1-(4-Cl-benzyl)-3-Cl- 4-(CF3-phenylamino)-1H-pyrrole-2,5-dione as a panspecific protein kinase inhibitor for inhibition of hematological complications in experimental chronic cholangitis in rats




pirole derivative, protein kinases inhibitor, chronic cholangitis, erythrocytes, leukocytes, platelets


The effect of a a panspecific inhibitor of pyrrole derivatives (1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1Hpyrrole- 2,5-dione, MI-1), synthesized at the Kyiv National Taras Shevchenko University, on hematological manifestations of experimental α-anaphthyl isothiocyanate-induced chronic cholangitis is studied. It is found that MI-1 reduces the level of inflammation, which is confirmed by the normalization of the total number of leukocytes in blood due to a decrease in the number of eosinophilic and neutrophilic granulocytes and lymphocytes involved in the development of experimental chronic cholangitis. MI-1 restores the number of erythrocytes in blood through the activation of erythropoiesis, that is evident by an increase in the number of reticulocytes in blood of rats with experimental cholangitis. MI-1 normalizes the number of platelets in blood most likely due to inhibition of platelet formation in bone marrow, activated by the development of an inflammatory process in liver. MI-1 reduces the level of hematological complications of experimental chronic cholangitis in rats and with proven low overall and hematoxicity and hepatoprotective effect is promising for further research as a compound with anti-inflammatory activity.


Galoosian, A., Hanlon, C., Zhang, J., Holt, E. W. & Yimam, K. K. (2020). Clinical updates in primary biliary cholangitis: trends, epidemiology, diagnostics, and new therapeutic approaches. J. Clin. Transl. Hepatol., 8, No. 1, pp. 49-60.

Pinto, C., Giordano, D. M., Maroni, L. & Marzioni M. (2018). Role of inflammation and proinflammatory cytokines in cholangiocyte pathophysiology. Biochim. Biophys. Acta. Mol. Basis. Dis., 1864, Iss. 4, Pt. B, pp. 1270-1278.

Gidwaney, N. G., Pawa, S. & Das K. M. (2017). Pathogenesis and clinical spectrum of primary sclerosing cholangitis. World. J. Gastroenterol., 23, No. 14, pp. 2459-2469.

Weiss, G., Ganz, T. & Goodnough, L. T. (2019). Anemia of inflammation. Blood, 133, No. 1, pp. 40-50. https://

Kuznietsova, H. M., Dziubenko, N. V., Lynchak, O. V., Tykhoniuk, O. I., Milokhov, D. S., Khilya, O. V. & Rybalchenko, V. K. (2018). Hepatoprotective effect of protein kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4- (CF3-phenylamino)-1H-pyrrole-2,5-dione on rats’ acute cholangitis. Dopov. Nac. akad. nauk Ukr., No. 5, pp. 83-90.

Fickert, P., Pollheimer, M. J., Beuers, U., Lackner, C., Hirschfield, G., Housset, C., Keitel, V., Schramm, С., Marschall, H.-U., Karlsen, T.H., Melum, E., Kaser, A., Eksteen, B., Strazzabosco, M., Manns, M. & Trauner, M. (2014). Characterization of animal models for primary sclerosing cholangitis (PSC). J. Hepatol., 60, No. 6, pp. 1290-1303.

Snook, J. A., Chapman, R. W., Sachdev, G. K., Heryet, A., Kelly, P. M., Fleming, K. A. & Jewell D. P. (1989). Peripheral blood and portal tract lymphocyte populations in primary sclerosing cholangitis. J. Hepatol., 9, No. 1, pp. 36-41.

Tsuneyama, K., Baba, H., Morimoto, Y., Tsunematsu, T. & Ogawa H. (2017). Primary biliary cholangitis: its pathological characteristics and immunopathological mechanisms. J. Med. Invest., 64, No. 1.2, pp. 7-13.

Fragulidis, G. P., Vezakis, A. I., Kontis, E. A., Pantiora, E. V., Stefanidis, G. G., Politi, A. N., Koutoulidis, V. K., Mela, M. K. & Polydorou, A. A. (2016). Eosinophilic cholangitis — a challenging diagnosis of benign biliary stricture: a case report. Medicine (Baltimore), 95, No. 1, e2394. MD.0000000000002394

Byelinska, I. V., Kuznietsova, H. M., Dziubenko, N. V., Lynchak, O. V., Rybalchenko, T. V., Prylutskyy, Yu. I., Kyzyma, O. A., Ivankov, O., Rybalchenko, V. K. & Ritter U. (2018). Effect of С60 fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats. Mater. Sci. Eng. C Mater. Biol. Appl., 93, pp. 505-517.

Kapellos, T. S., Bonaguro, L., Gemünd, I., Reusch, N., Saglam, A., Hinkley, E. R. & Schultze J. L. (2019). Human monocyte subsets and phenotypes in major chronic inflammatory diseases. Front. Immunol., 10, 2035.

Byelinska, I. V., Lynchak, O. V., Rybalchenko, T. V., Yablonska, S. V., Bahurynska, O. M. & Rybalchenko, V. K. (2015). Morphofunctional parame ters of blood cells of a rat with 1,2-dimethylhydrazi ne-induced colon carcino genesis. Cytol. Genet., 49, No. 3, pp. 158-164.

Scott, M. K. D., Quinn, K., Li, Q., Carroll, R., Warsinske, H., Vallania, F., Chen, S., Carns, M. A., Aren, K., Sun, J., Koloms, K., Lee, J., Baral, J.., Kropski, J., Zhao, H., Herzog, E., Martinez, F. J., Moore, B. B., Hinchcliff, M., Denny, J., Kaminski, N., Herazo-Maya, J. D., Shah, N. H. & Khatri, P. (2019). Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study. Lancet. Respir. Med., 7, pp. 497-508.

Byelinska, I. V., Rybalchenko, T. V., Tsyvinska, S. M. & Rybalchenko, V. K. (2017). The hematological effects of the protein kinases inhibitor maleimide derivative and 5-fluorouracil. Fiziol Zh., 63, No. 4, pp. 37-47 (in Ukrainian).

Joshi, N. & Rajeshwari, K. (2009). Deflazacort. J. Postgrad. Med., 55, Iss. 4, pp. 296-300. https://doi. org/10.4103/0022-3859.58942

Lisman, T. & Luyendyk, J. P. (2018). Platelets as modulators of liver diseases. Semin. Thromb. Hemost., 44, No. 2, pp. 114-125.



How to Cite

Byelinska І., Kuznietsova Г., Dziubenko Н., Savych Ю., Milokhov Д., Khilya О., & Rybalchenko Т. (2021). Application of 1-(4-Cl-benzyl)-3-Cl- 4-(CF3-phenylamino)-1H-pyrrole-2,5-dione as a panspecific protein kinase inhibitor for inhibition of hematological complications in experimental chronic cholangitis in rats. Reports of the National Academy of Sciences of Ukraine, (4), 94–102.