Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body
Most pharmaceutical substances interact with several or even many molecular targets in the organism, determining the complex profiles of their biological activity. Moreover, due to biotransformation in the human body, they form one or several metabolites with different biological activity profiles....
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/20/7492 |
| _version_ | 1797551373542227968 |
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| author | Dmitry A. Filimonov Anastassia V. Rudik Alexander V. Dmitriev Vladimir V. Poroikov |
| author_facet | Dmitry A. Filimonov Anastassia V. Rudik Alexander V. Dmitriev Vladimir V. Poroikov |
| author_sort | Dmitry A. Filimonov |
| collection | DOAJ |
| description | Most pharmaceutical substances interact with several or even many molecular targets in the organism, determining the complex profiles of their biological activity. Moreover, due to biotransformation in the human body, they form one or several metabolites with different biological activity profiles. Therefore, the development and rational use of novel drugs requires the analysis of their biological activity profiles, taking into account metabolism in the human body. In silico methods are currently widely used for estimating new drug-like compounds’ interactions with pharmacological targets and predicting their metabolic transformations. In this study, we consider the estimation of the biological activity profiles of organic compounds, taking into account the action of both the parent molecule and its metabolites in the human body. We used an external dataset that consists of 864 parent compounds with known metabolites. It is shown that the complex assessment of active pharmaceutical ingredients’ interactions with the human organism increases the quality of computer-aided estimates. The toxic and adverse effects showed the most significant difference: reaching 0.16 for recall and 0.14 for precision. |
| first_indexed | 2024-03-10T15:43:47Z |
| format | Article |
| id | doaj.art-cc3c28e29bdb4016b57d900eec9a4fcf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:43:47Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cc3c28e29bdb4016b57d900eec9a4fcf2023-11-20T16:38:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120749210.3390/ijms21207492Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human BodyDmitry A. Filimonov0Anastassia V. Rudik1Alexander V. Dmitriev2Vladimir V. Poroikov3Laboratory of Structure-Function Based Drug Design, Department of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya Str., 10, bldg. 8, 119121 Moscow, RussiaLaboratory of Structure-Function Based Drug Design, Department of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya Str., 10, bldg. 8, 119121 Moscow, RussiaLaboratory of Structure-Function Based Drug Design, Department of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya Str., 10, bldg. 8, 119121 Moscow, RussiaLaboratory of Structure-Function Based Drug Design, Department of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya Str., 10, bldg. 8, 119121 Moscow, RussiaMost pharmaceutical substances interact with several or even many molecular targets in the organism, determining the complex profiles of their biological activity. Moreover, due to biotransformation in the human body, they form one or several metabolites with different biological activity profiles. Therefore, the development and rational use of novel drugs requires the analysis of their biological activity profiles, taking into account metabolism in the human body. In silico methods are currently widely used for estimating new drug-like compounds’ interactions with pharmacological targets and predicting their metabolic transformations. In this study, we consider the estimation of the biological activity profiles of organic compounds, taking into account the action of both the parent molecule and its metabolites in the human body. We used an external dataset that consists of 864 parent compounds with known metabolites. It is shown that the complex assessment of active pharmaceutical ingredients’ interactions with the human organism increases the quality of computer-aided estimates. The toxic and adverse effects showed the most significant difference: reaching 0.16 for recall and 0.14 for precision.https://www.mdpi.com/1422-0067/21/20/7492drug-like compoundsbiological activity profilesmetabolismcomputer-aided predictions |
| spellingShingle | Dmitry A. Filimonov Anastassia V. Rudik Alexander V. Dmitriev Vladimir V. Poroikov Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body International Journal of Molecular Sciences drug-like compounds biological activity profiles metabolism computer-aided predictions |
| title | Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body |
| title_full | Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body |
| title_fullStr | Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body |
| title_full_unstemmed | Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body |
| title_short | Computer-Aided Estimation of Biological Activity Profiles of Drug-Like Compounds Taking into Account Their Metabolism in Human Body |
| title_sort | computer aided estimation of biological activity profiles of drug like compounds taking into account their metabolism in human body |
| topic | drug-like compounds biological activity profiles metabolism computer-aided predictions |
| url | https://www.mdpi.com/1422-0067/21/20/7492 |
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