Normal and Neoplastic Hematopoiesis, Organs of immune response, Targeted anticancer therapy, multikinase inhibitors, chemical substances toxicology, experimental models of cancers or anemia.

Previous and Current Research

We are focused on hematological effects and action mechanisms of antitumor and antianemic compounds, mechanisms of carcinogenesis, tumor-associated changes in hematopoiesis, morphofunctional state of neoplastic cells of hemopoietic origin and organs of immune response.

Maleimide derivatives (MI-1) and Pyrrole derivatives (D-1) was in silico designed and synthesized by professor Yulian Volovenko team (Chemistry Faculty, Taras Shevchenko National University of Kyiv) as a competitive inhibitor of the ATP-binding site of protein kinases (Fig. 1).

Figure 1. (A) 3-chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and (B) 5-amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one (D-1) formulas.

MI-1 suppresses proliferative activity of human neoplastic monoblast U-937 cells, causes block cells in G0/G1 phase, and represses mitotic activity and induces apoptosis (Fig. 2) in micromolar concentrations.

MI-1 inhibits VEGF-R, FGF-R, EGF-R and PDK1, Src, Syk and other protein kinases and is multikinase inhibitors. VEGF-R, PDK1, Syk and others kinases are highly expressed in different subtype of acute myeloid leukemia. Blocking of these kinases by MI-1 suppresses leukemia cells growth and eliminates them by apoptosis as is shown in the results of our investigation.

Moreover, MI-1 suppresses colon cancer growth in vivo as was shown in chemically induced experimental colon carcinogenesis.

MI-1 impact on normal hematopoiesis after different doses injection and terms of expose was investigated. Low general toxicity and hematotoxicity towards leukopoiesis, erythropoiesis and thrombopoiesis after chronic expose and subchronic administration of the doses, five and ten times exceeding the effective antitumor one, was shown (Fig. 3).

Thus, MI-1 as targeted multikinase inhibitor with low toxicity is promising compound for myeloid leukemia treatment.

Methodological and Technical Expertise

Toxicology, Hematology, leukemogenesis, carcinogenesis, immune response, histology, cells biology.

Collaboration:

National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine, Kyiv (Ukraine)

National Cancer Institute of Ukraine, Kyiv (Ukraine)

Projects

2019-01 to 2021-12 | Grant Ministry of Education and Science of Ukraine (Kyiv, UA). Part of  GRANT_NUMBER: 0119U100331. The latest hybrid antitumors and anti-inflammatory nanocomplexes based on pyrrole and fullerene C60: creation, characteristics, pharmacodynamics and toxicological characteristics

2017-04 to 2018-12 | Grant Ministry of Education and Science of Ukraine (Kyiv, UA)

Part of GRANT_NUMBER: 0116U002639. Pyrrole derivatives as anti-inflammatory and anti-tumor compounds of new generation.

2011-01 to 2015-12 | Grant Ministry of Education and Science of Ukraine (Kyiv, UA)

Part of GRANT_NUMBER: 0111U004648. Mechanisms for implementation of adaptive-compensatory reactions of the organism in the development of various pathologies

Team:

Halyna Kuznietsova

Natalia Dziubenko

Yulia Savych

Mykola Kravchenko

Selected Publications

Contacts

Phone: +380503308221  

E-mail: iryna.byelinska@knu.ua, byelinska@ukr.net