Criteria of toxicity of biologically active molecules on the example of complex copper compound with phenanthroline using the method of dynamic speckle interferometry
Abstract:
According to literature data, organometallic compounds have antitumour activity, but some of them, such as platinum compounds, have various side effects. Evaluation of medicinal products is performed according to the Order of the Ministry of Health of the Russian Federation dated 16.10.1997 N 305 "On the norms of variations permissible in the manufacture of medicinal products and packaging of industrial products in pharmacies" (together with the "Instruction on quality assessment of medicinal products manufactured in pharmacies"). At the same time, the search for alternative, simple, informative, cheap and accurate methods of assessing in vitro properties is the most important and still unresolved task.For the complex compound of copper with phenanthroline obtained in this research with concentrations of reagents at the level of MAC in water the possibility of using the method of dynamic speckle-interferometry to assess toxicity on different cell cultures was shown: when the toxicity of the complex compound decreases in comparison with copper sulphate and with phenanthroline there is an increase in the intensity of processes occurring in the cell. The experimental data correlate with the data on the lipophilicity of the complex compound of copper with phenanthroline, which was determined by the method of Quantitative Structure Activity Correlation (QSAC), using the computer programme Molinspiration. The influence of different substituted amino acids (glycine, alanine, serine, asparagic acid, asparagine, glutamic acid, glutamine) on this property was also evaluated: the introduction of amino acid decreases the value of lipophilicity in comparison with the complex compound of copper with phenanthroline, which according to the Lipinski criterion reduces the toxicity of these compounds.
Keywords:antitumour drugs, complex compounds, biologically active molecules.
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