QSAR investigation of acute toxicity of organic compounds during oral administration to mice

Tinkov O.V.1 , Grigorev V.Yu.2, Polishchuk P.G.3, Yarkov A.V.2, Raevsky O.A.2

1. Military Institute of the Ministry of Defense, Tiraspol, Moldova
2. Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Russia
3. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
Section: Bioinformatics and Chemoinformatics
DOI: 10.18097/PBMC20196502123      PubMed Id: 30950817
Year: 2019  Volume: 65  Issue: 2  Pages: 123-132
The effect of the structure of organic compounds on the acute toxicity upon oral injection in mice was studied using 2D simplex representation of the molecular structure and Random forest (RF) methods. Satisfactory quantitative structure-activity relationship (QSAR) models were constructed (R2 test = 0,61–0,62). The interpretation of the obtained QSAR models was carried out. The contributions of known toxicophores with established mechanisms of action were calculated in order to confirm the ability of the interpretation approach to correctly rank them relative to other structural fragments. The influence of the molecular surroundings of some toxicophores was analyzed. We analyzed the contributions of other highly ranked fragments from the list of common functional groups and ring systems in order to find new potential toxicophores. The on-line version of the expert system “OCHEM” (https://ochem.eu) and Arithmetic Mean Toxicity (AMT) approach were used for a comparative QSAR study.
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Keywords: toxicity, QSAR, structure-property modeling, simplex descriptors, random forest, structural interpretation
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Tinkov, O. V., Grigorev, V. Yu., Polishchuk, P. G., Yarkov, A. V., Raevsky, O. A. (2019). QSAR investigation of acute toxicity of organic compounds during oral administration to mice. Biomeditsinskaya Khimiya, 65(2), 123-132.
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