ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes
The development of new substances with the ability to interact with a biological target is only the first stage in the process of the creation of new drugs. The 5-nitroisatin derivatives considered in this study are new inhibitors of cyclin-dependent kinase 2 (CDK2) intended for anticancer therapy....
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| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/11/3019 |
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| author | Przemysław Czeleń Tomasz Jeliński Agnieszka Skotnicka Beata Szefler Kamil Szupryczyński |
| author_facet | Przemysław Czeleń Tomasz Jeliński Agnieszka Skotnicka Beata Szefler Kamil Szupryczyński |
| author_sort | Przemysław Czeleń |
| collection | DOAJ |
| description | The development of new substances with the ability to interact with a biological target is only the first stage in the process of the creation of new drugs. The 5-nitroisatin derivatives considered in this study are new inhibitors of cyclin-dependent kinase 2 (CDK2) intended for anticancer therapy. The research, carried out based on the ADMET (absorption, distribution, metabolism, excretion, toxicity) methods, allowed a basic assessment of the physicochemical parameters of the tested drugs to be made. The collected data clearly showed the good oral absorption, membrane permeability, and bioavailability of the tested substances. The analysis of the metabolite activity and toxicity of the tested drugs did not show any critical hazards in terms of the toxicity of the tested substances. The substances’ low solubility in water meant that extended studies tested compounds were required, which helped to select solvents with a high dissolving capacity of the examined substances, such as DMSO or NMP. The use of aqueous binary mixtures based on these two solvents allowed a relatively high solubility with significantly reduced toxicity and environmental index compared to pure solvents to be maintained, which is important in the context of the search for green solvents for pharmaceutical use. |
| first_indexed | 2024-03-09T17:00:03Z |
| format | Article |
| id | doaj.art-b612f77e75924c3eb6fa7f6e7ed52f7e |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T17:00:03Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b612f77e75924c3eb6fa7f6e7ed52f7e2023-11-24T14:31:11ZengMDPI AGBiomedicines2227-90592023-11-011111301910.3390/biomedicines11113019ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 EnzymesPrzemysław Czeleń0Tomasz Jeliński1Agnieszka Skotnicka2Beata Szefler3Kamil Szupryczyński4Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096 Bydgoszcz, PolandDepartment of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096 Bydgoszcz, PolandFaculty of Chemical Technology and Engineering, Bydgoszcz University of Science and Technology, Seminaryjna 3, 85-326 Bydgoszcz, PolandDepartment of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096 Bydgoszcz, PolandDoctoral School of Medical and Health Sciences, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jagiellońska 13, 85-067 Bydgoszcz, PolandThe development of new substances with the ability to interact with a biological target is only the first stage in the process of the creation of new drugs. The 5-nitroisatin derivatives considered in this study are new inhibitors of cyclin-dependent kinase 2 (CDK2) intended for anticancer therapy. The research, carried out based on the ADMET (absorption, distribution, metabolism, excretion, toxicity) methods, allowed a basic assessment of the physicochemical parameters of the tested drugs to be made. The collected data clearly showed the good oral absorption, membrane permeability, and bioavailability of the tested substances. The analysis of the metabolite activity and toxicity of the tested drugs did not show any critical hazards in terms of the toxicity of the tested substances. The substances’ low solubility in water meant that extended studies tested compounds were required, which helped to select solvents with a high dissolving capacity of the examined substances, such as DMSO or NMP. The use of aqueous binary mixtures based on these two solvents allowed a relatively high solubility with significantly reduced toxicity and environmental index compared to pure solvents to be maintained, which is important in the context of the search for green solvents for pharmaceutical use.https://www.mdpi.com/2227-9059/11/11/3019isatinCDK2competitive inhibitionADMETsolubilitycosolvation |
| spellingShingle | Przemysław Czeleń Tomasz Jeliński Agnieszka Skotnicka Beata Szefler Kamil Szupryczyński ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes Biomedicines isatin CDK2 competitive inhibition ADMET solubility cosolvation |
| title | ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes |
| title_full | ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes |
| title_fullStr | ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes |
| title_full_unstemmed | ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes |
| title_short | ADMET and Solubility Analysis of New 5-Nitroisatine-Based Inhibitors of CDK2 Enzymes |
| title_sort | admet and solubility analysis of new 5 nitroisatine based inhibitors of cdk2 enzymes |
| topic | isatin CDK2 competitive inhibition ADMET solubility cosolvation |
| url | https://www.mdpi.com/2227-9059/11/11/3019 |
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