Modelling toxicity biologically active derivatives amides of pyridine carboxylic acids

  • L. S. Bobkova State institution «Institut of Pharmacology and Toxicology of National Medical Academy of Sciens of Ukraine», Kyiv
Keywords: modeling, toxicity, amides of pyridine carboxylic acids, «structure–toxicity»


At the present time attention is directed search for effective and non- toxic biologically active compounds. For search effective substances with the set properties requires thorough analysis and theoretical studies of primary experimental data with the use of modern information, computer technologies and mathematical modeling methods. In this regard, relevant studies are based on a theoretical evaluation of the peculiarities of interrelation «structure–toxicity».

A in of invention: The study of structural characteristics (descriptors) derivatives of pyridine, for which revealed analgesic activity for the modelling of acute toxicity as the basis to optimization of directional synthesis of new biologically active compounds.

Object of research are structural analogues of active compounds drugs Amizon and Nifenazon - derivatives of 3-(4)-pyridinecarboxylic acid amides. We used the methods of regression and discriminant analysis.  Descriptors what characterizing patterns of molecules calculated using the programs E-Dragon (> 1600 descriptors) after pre-optimize the geometry of molecules.

Using regression and discriminant analysis we studied interrelation on acute toxicity from 2D and 3D descriptors of pyridinecarboxylic acid amides. The dependence of acute toxicity from the structure of the derivatives pyridinecarboxylic acid amides described by a combination of descriptors Mor30m; Mor30p; G1p (R= 0.9503, R2=0.9031). According to the results of the discriminant analysis we found a combination of molecular descriptors, which allows with a high accuracy (100 %) to distribute pyridinecarboxylic acid amides in groups ranges LD50 from 5,045 to 2,712 mm/kg (the first group) and from 1,885 to 1,491 mm/kg (second group). Obtained one research data on the patterns of relationships between structure and toxicity, can be applied for evaluation of toxicity and search optimization and purposeful synthesis of new biologically active secure connections.


1. Bobkova L. S., Chekman I. S., Yavorovsky O. P. and others. Application of the QSAR method in toxicology // Sovrem. probl tox - 2008. - No. 2. - P.78-86.
2. Bukhtiarova T. A. Experimental substantiation of directions of search and study of new neopioid analgesics in a series of derivatives of nitrogen heterocycles. Dis ... Dr. Honey Sciences: 14.03.05 - Pharmacology / Institute of Pharmacology and Toxicology. - K., 1998. - 330 p.
3. Golovko Yu. S., Ivashkevich O. A., Matulis V. E., Gaponik P. N. Basic directions of computer modeling of biological activity of molecules // Chemical problems of creation of new materials and technologies: Cb. Art. - 2008 - no. 3. - pp. 144-164. [Electronic resource]. - Access mode: http: /
4. Yerina AM Statistical simulation and forecasting. - K .: KNEU, 2001. - 170 p.
5. Zartrudina R. S., Kornaukhova MA Conformational and isomeric analysis of amides of pyridinecarboxylic acids // Vestn. Volgograd State University - 2012. - Aug. 10, Vip. 6. - P. 57-61.
6. Karkishchenko NN, "Classic and alternative models in drug toxicology" // Biomedicine. - 2006. - No. 4. - P. 5-23.
7. Lukewitz E. Derivatives of pyridine in the arsenal of drugs (review) // Chemistry of heterocycle. union - 1995.- No. 6. - P. 723-734.
8. Syroeshkin AV, Stepanova N. A., Popov P. I., et al. Forecasting of toxicity of chemical compounds of the group of antituberculous drugs by the method of quantitative correlations structure-activity // Forensic medical examination. - 2009. - 5 p. [Electronic resource]. - Access mode:
9. Testing on animals. [Electronic resource]. - Mode of access: of animals.
10. Tik'kov O.V., Polyshchuk P.G., Artemenko A.G., etc. Investigation of acute toxicity of esters on the basis of a 2D-simplex representation of a molecular structure // Journal of Siberian Federal University. Chemistry 1 - 2013. - N 6. - P. 65-75.
11. Cho C. W., Ranke J., Arning J. et al. In silico modeling for predicting the cationic hydrophobicity and cytotoxicity of ionic liquids towards Leukemia rat cell line, Vibrio fischeri and Scenedesmus vacuolatus based on molecular interaction potentials of ions // SAR QSAR Environ. Res - 2013. - V. 24, N 10. - P. 863-882.
12. Kim J., Kim S., Schaumann G. E. Development of a QSAR-based two-stage prediction model for estimating mixture toxicity // SAR QSAR Environ. Res - 2013. - V. 24, N 10. - P. 841-861.
13. Todeschini R., Consonni. V. Handbook of molecular descriptors. -Wiley-VCH: Weinheim, 2000.
How to Cite
Bobkova, L. S. (2019). Modelling toxicity biologically active derivatives amides of pyridine carboxylic acids. Farmatsevtychnyi Zhurnal, (4), 90-100. Retrieved from
General and Clinical Pharmacology