Study of biological activity of doxorubicin conjugate with nacetyl- D-galactosamine hydrasonic linker

The cytotoxicity of the synthesized conjugate was assessed in the cultivated Huh7 cells using the MTT test in co-incubation for 72 h in the concentration range from 4×10-2 µg/ml to 10 µg/ml. The toxicity was tested in vivo in the female DBA2 mice by an intraperitoneal injection of the test conjugate at a dose of 20 mg/kg, 25 mg/kg and 33 mg/kg (water for injectionused to dilute) followed by observation of the animals for 28 days. The DBA2 strain mice were intraperitoneally transplanted with the lymphocytic leukemia L1210 to study the antitumor activity of the above agent. The conjugate was administered at a dose of 24 or 12 mg/kg once 24 hours after the tumor transplantation. The efficacy was assessed by the criterion of increased survival (IS), and tolerability was evaluated by changes in the body weight of mice, some external signs, and the number of animals’ deaths from toxicity. Results. The IC50 values in the cultivated Huh7 cells were recorded to be 0.08±0.02 µg/ml. The doses tested in the mice did not show any toxic effects within 672 hours after the single dose use; no death cases in the mice were reported, and no special features were recorded in the autopsy. The maximum tolerated dose was determined to be above 33 mg / kg for the intraperitoneal administration. In the model of the lymphocytic leukemia L1210, the IS value was 60% (p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }