Vol 16, No 2 (2017)

Introduction. Search of active compounds among cyphetrylin analogues is one of prospective directions in synthesis of new compounds that have higher resistance to fermentation. The report I presented the synthesis of new cyphetrylin compounds with various functional substituents (thiazolidin, naphthyl, rimantadine, chlorophenacyl and cyphelin), their presence on the surface of tumor cells when binding to receptors would enhance the cytotoxic effect of modified cyphetrylin compounds on tumor. Objective. The study of anti-tumor activity of the synthesized analogues cyphetrylin modified by cytotoxic agents. Materials and methods. The research was carried out on the transplanted murine tumors: breast adenocarcinoma Ca-755 and melanoma B-16. Drug solutions were prepared ex tempore with the use of dimethylsulfoxide or ethanol diluted with saline to a concentration of 10 % and was administered to female mice-hybrids F1 (C57Bl/6 х DBA/2) daily subcutaneous injection in doses of 5, 10, 20 and/or 30 mg/kg for 5 days. The criteria of antitumor effect served the tumor growth inhibition (TGI, %) and the increase in lifespan (ILS, %) of test animals compared to the controlled. Results. Boc-Cys(Thp) - Phe-D-Trp-Lys(ClPhe) - Thr-OMe - pentapeptide modified by chlorophenacyl lysine at N^c-group in a dose of 5 mg/kg on breast adenocarcinoma Ca-755showed a short-term antitumor effect directly after the end of the treatment (TGI = 73 %). Boc-Phe-D-Trp-Lys (Ac-Sar-Val) - Thr-OMe - tetrapeptide modified by cyphelin lysine at №-group in a dose of 10 mg/kg caused melanoma B-16 growth inhibition for 75-85 % within 4 days after the end of the treatment and increased lifespan (ILS) of mice for 29 %. Conclusion. 2 of 7 cyphetrylin analogues, modified by cytotoxic agents, showed antitumor activity, that indicate the prospects for their further research as antitumor compounds on other tumor models.

Introduction. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP А1) and other RNA-binding proteins involved in splicing participate in realization of genetic information and can be greatly changed in pathological conditions including tumors. Objective. Proteomic study of hnRNP A1 and other RNA-binding splicing proteins in 10 human malignant and non-malignant cultured cell lines of mesenchymal and epithelial origin. Materials and methods. Two-dimensional gel electrophoresis of adenocarcinomas (LNCaP, DU-145, PC-3, 769-P) and sarcomas (U2-OS, SK-UT-1B, RD) cell lines with following protein identification by matrix-assisted laser desorption ionization mass spectrometry have been carried out. Results. HnRNP А1 has been identified as an abundant protein in all studied malignant cell lines. It has been revealed in lower amount in normal mesenchymal cells compared to malignant cultured cells and achieved undetectable levels in myoblasts after induction of differentiation. Conclusion. High cellular level of hnRNP А1 can suggest high proliferative activity of cells including malignant those. Hence, hnRNP А1 and other RNA-binding splicing proteins hold promise to its further investigation in human transformed cells.

Introduction. The perspective direction in therapy of dyslipidemia (DLP) is a complex application of biologycally active substances from marine hydrobionts. Objective. The purpose of research - to compare the lipidcorrective action of preparates based on biologically active substances from marine hydrobionts - fukolam and maristim - individually and in combination with atorvastatin in patients with DLP. Materials and methods. 250patients with DLP and 40 healthy donors were included in research. As medicines atorvastatin, fukolam, maristim were used. In the blood serum the levels of lipid spectrum were determined. Results. Hypolipidemic action of fukolam in complex of basic therapy of patients with DLP was implemented by gradually reducing the total cholesterol, cholesterol of low-density lipoproteins, triglycerides levels to control values. The efficacy of fukolam was comparable with that of atorvastatin in a daily dose of 10 mg. Complex of «fukolam-maristim» showed hypolipidemic effect in severe hyperlipidemia. Conclusions. Combined therapy with use of bioactive substances of natural origin may be one of the way to improve the efficiency of hypolipidemic therapy. We have developed the algorithm of differential correction of DLP by inclusion the fukolam and maristim in complex therapy.