A novel nano-formulation of the anticancer drug cisplatin (Cis) with C 60 fullerene (C 60 +Cis complex) was developed, demonstrating enhanced cytotoxic activity towards tumor cell lines in vitro n comparison to Cis alone. The enhanced proapoptotic activity of the novel complexes was found to be tightly connected with their unique capability to circumvent cancer drug resistance in vitro, as revealed by investigation of human leukemia cells HL-60 together with their sublines resistant towards doxorubicin (HL-60/adr, multidrug resistance protein-1=MRP-1=ABCC1 overexpressing) and vincristine (HL-60/vinc, P-glycoprotein=P-gp=ABCB1 overexpressing). The enhanced anticancer activity of the developed С 60 +Cis complexes was also confirmed in vivo on male C57BL/6J mice bearing Lewis lung carcinoma, effectively inhibiting tumor growth and formation of metastases in comparison to free single Cis. For better understanding of molecular mechanisms underlying the potential ability of the С 60 +Cis complexes to circumvent cancer drug resistance, a molecular docking study was conducted. This analysis demonstrated the potential capability of C 60 fullerene to form van der Waals interactions with potential binding sites of P-gp, MRP-1and MRP-2 (ABCC2) molecules, with maximum affinity to MRP-2. The observed phenomenon might indicate the mechanism how the C 60 +Cis complex bypasses drug resistance of cancer cells by direct binding to ABC transporter proteins. Additionally, the results of Ames mutagenicity test demonstrated that immobilization of Cis on С 60 fullerene significantly diminishes mutagenic activity of Cis and may reduce the probability of secondary neoplasms induction. Concluding, the synthesized C 60 +Cis complex effectively induces cancer cell death in vitro and inhibits tumor growth in vivo, circumventing cancer cell resistance to chemotherapy due to the specific affinity of C 60 fullerene towards ABC-transporter proteins. The obtained results indicate the C 60 +Cis complex as a promising novel chemotherapeutic agentespecially for treatment of drug-resistant tumors.

To study an anticancer activity and to measure cytological and enzymatic indicators of general toxicity of 4-thiazolidinone-based compounds (Les-3288, Les-3833) in the NK/Ly lymphoma grafted to BALB/C mice. Methods. BALB/C mice were implanted with the ascitic NK/ Ly lymphoma and treated for 14 days with 4-thiazolidinone derivatives-Les-3833 (2.5 mg/kg of bodyweight), Les-3288 (5 mg/kg of bodyweight), a complex of Les-3833 with the polymeric nanocarrier Les-3833+PNC (2.5 mg/kg of bodyweight) in water, and doxorubicin (1 mg/kg of bodyweight) used as a positive control. The lymphoma development was monitored by measuring the amount of ascitic fluid in the treated mice. The effects of the applied compounds were checked after 35 days of tumor growth. Results. A distinct decrease in the amount of the ascite fluid with lymphoma cells was revealed in the treated mice, while a 1.5-fold increase of its amount was detected in the untreated mice of control group. The 4-thiazolidinone derivatives demonstrated much less toxicity, and erythrocytes count stayed normal after 21 days of animal treatment. The development of NK/Ly lymphoma led to an increase in the neutrophils number, while the applied anticancer compounds reduced it significantly. Les-3833 and Les-3288 did not affect the number of lymphocytes over the normal level. The activity of aspartate and alanine aminotransferases in blood serum was elevated on the 14 day of treatment, and returned to the normal level on the 21 day. Conclusion. Novel 4-thiazolidinones Les-3833 and Les-3288 are effective in the treatment of NK/Ly lymphoma grafted to BALB/C mice. These derivatives induced had limited negative side effects in the treated mice.

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To determine cytotoxic effects towards a tumor cells culture of the heterocyclic derivative conjugated with lectins of different carbohydrate specificity. Methods. Conjugation of lectins (Pea seeds (PSA), peanuts (PNA) and erythroagglyutinin from bean seeds (PHA-E) with thiopyrano[2,3-d]thiazole Les-1895, biotesting these conjugates in the cell culture. Results. The conjugates of Les-1895 with specific lectins posses increased cytotoxic effects towards Jurkat cells-by 23 % for PSA-Les-1895, 34 % for PNA-Les-1895, and by 12 % for PHA-E-Les-1895. IC 50 of Les-1895 conjugates was ≈ 10 μg/ml, whereas at using free Les-1895-it was ≈ 30 μg/ml. The PNA and PHA-E conjugates with Les-1895 suppressed the viability of HCT 116 cells more considerably than the PSA conjugate. A cytotoxic action of PNA (IC 50 = 4 μg/ml) and PHA-E (IC 50 = 3 μg/ml) conjugates was more pronounced than the effect of free Les-1895 (IC 50 = 10 μg/ml) or intact lectins. The conjugation of Les-1895 with human serum albumin (HSA) increased the water solubility, however, such conjugation decreased the cytotoxic effect towards Jurkat cells by 40 %. The pseudonormal cells line HEK 293 was less sensitive to the action of native lectins-PSA, PNA and PHA-E as well as to the action of conjugates of these lectins. Conclusions. Conjugation of Les-1895 with specific lectins enhanced a cytotoxic effect. The obtained results suggest a possibility of the addresed delivery of biologically active compounds to specific cells of tissues and organs of the human body.