Theoretical study of a series of phenol derivatives: molecular properties vs. cytotoxicity

The quantum chemical calculations using DFT were performed for 2-alkyl-4X and 2,6-dialkyl-4-X substituted phenols. Based on the optimal geometries the bond dissociation enthalpies (BDEs), proton enthalpies (PAs) and the lipophilicities were computed. Additionally, simple geometry parameter was found correlating well with experimental leukemia cell toxicity of substituted phenols. Next, we have found no linear dependence between PA or BDE values and log1/C values in gas phase or in water despite the radical toxicity mechanism proposed in the literature.

Antitumor activity of Ormustine against transplanted leukemia in mice

Objective: Evaluation of antitumor activity of a novel alkylnitrosoureas derivative Ormustine (an alkylnitrosocarbamoyl L-ornithine) in mouse lymphoid leukemia models. Materials and methods Antitumor activity of Ormustine has been evaluated in B6D2F1 mice with ascites form of leukemia (L1210, L1210/arenosa, L1210/citrullin and P388) and the solid (P388) form. In this study we used preparations from the alkylnitrosourea group: Ormustine, Aranoza and Lizomustine. Treatment of animals was started 24 hours after inoculation of leukemia intraperitoneally, and 48 hours after inoculation subcutaneous P388. Drugs in a wide range of doses were administrated once intravenously. The follow up period of the animals continued until their death. Criteria of antitumor effect were increasing life expectancy and cure. Evaluation criteria of antitumor effect was the increase in life of experimental mice compared to control ones. Results. Antitumor activity of a novel alkylnitrosoureas derivative, Ormustine has been studied in vivo on the growth of transplanted lymphoid leukemia, such as L1210 (ascites version) and P388 (ascites and solid tumor). Effective dose of single intravenous injection Ormustine against lymphoid leukemia L1210 and P388 was 125 mg/kg. The drug effectively inhibited growth of experimental leukemia. The significant part of the mice with limfoleukemia has been cured. We have also established the single intravenous therapeutic dose of Ormustine on L1210 and Р388 leukemia - 125mg/kg of body weight. Conclusion. The data obtained characterizes Ormustin as a promissing anticancer drug.

Liver Mitochondrial Enzyme System In The Dynamics Of Experimental Leukemia

In rats with leukemia activity of liver mitochondrial enzymes are decreased at 6 months. Later, we noted compensatory activation of complexes II and III of the respiratory chain and transition to decompensation stage by final deadline. The activity of complex IV of the respiratory chain remains high. These changes result from increased lipid peroxidation and decreased activity of antioxidant protection enzymes.