Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids
Free radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the five different coumarin derivatives have been investigated. In the tests of potential toxicity, all com...
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Marko R. Antonijević Edina H. Avdović Dušica M. Simijonović Žiko B. Milanović Ana D. Amić Zoran S. Marković |
| author_facet | Marko R. Antonijević Edina H. Avdović Dušica M. Simijonović Žiko B. Milanović Ana D. Amić Zoran S. Marković |
| author_sort | Marko R. Antonijević |
| collection | DOAJ |
| description | Free radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the five different coumarin derivatives have been investigated. In the tests of potential toxicity, all compounds exhibited low toxicity with significant antioxidative potential at the same time. In this paper, the radical scavenging activity of the abovementioned coumarin derivatives towards ten different radical species was investigated. It was found that all investigated compounds show good radical scavenging ability, with results that are in correlation with the results published in the previous study. Three additional mechanisms of radical scavenging activity were investigated. It was found that all three mechanisms are thermodynamically plausible and in competition. Interestingly, it was found that products of the Double Hydrogen Atom Transfer (DHAT) mechanism, a biradical species in triplet spin state, are in some cases more stable than singlet spin state analogues. This unexpected trend can be explained by spin delocalisation over the hydrazide bridge and phenolic part of the molecule with a low probability of spin pairing. Besides radical-scavenging activity, the pharmacokinetic and drug-likeness of the coumarin hybrids were investigated. It was found that they exhibit good membrane and skin permeability and potential interactions with P-450 enzymes. Furthermore, it was found that investigated compounds satisfy all criteria of the drug-likeness tests, suggesting they possess a good preference for being used as potential drugs. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:37:20Z |
| publishDate | 2022-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1a435ccda56a44338f86bb2bbf88ecb52023-11-23T11:40:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123149010.3390/ijms23010490Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide HybridsMarko R. Antonijević0Edina H. Avdović1Dušica M. Simijonović2Žiko B. Milanović3Ana D. Amić4Zoran S. Marković5Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaDepartment of Chemistry, Josip Juraj Strossmayer University of Osijek, Ulica Cara Hadrijana 8A, 31000 Osijek, CroatiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaFree radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the five different coumarin derivatives have been investigated. In the tests of potential toxicity, all compounds exhibited low toxicity with significant antioxidative potential at the same time. In this paper, the radical scavenging activity of the abovementioned coumarin derivatives towards ten different radical species was investigated. It was found that all investigated compounds show good radical scavenging ability, with results that are in correlation with the results published in the previous study. Three additional mechanisms of radical scavenging activity were investigated. It was found that all three mechanisms are thermodynamically plausible and in competition. Interestingly, it was found that products of the Double Hydrogen Atom Transfer (DHAT) mechanism, a biradical species in triplet spin state, are in some cases more stable than singlet spin state analogues. This unexpected trend can be explained by spin delocalisation over the hydrazide bridge and phenolic part of the molecule with a low probability of spin pairing. Besides radical-scavenging activity, the pharmacokinetic and drug-likeness of the coumarin hybrids were investigated. It was found that they exhibit good membrane and skin permeability and potential interactions with P-450 enzymes. Furthermore, it was found that investigated compounds satisfy all criteria of the drug-likeness tests, suggesting they possess a good preference for being used as potential drugs.https://www.mdpi.com/1422-0067/23/1/490radical scavengingantioxidantscoumarinsDFTpharmacokinetics |
| spellingShingle | Marko R. Antonijević Edina H. Avdović Dušica M. Simijonović Žiko B. Milanović Ana D. Amić Zoran S. Marković Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids International Journal of Molecular Sciences radical scavenging antioxidants coumarins DFT pharmacokinetics |
| title | Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids |
| title_full | Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids |
| title_fullStr | Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids |
| title_full_unstemmed | Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids |
| title_short | Radical Scavenging Activity and Pharmacokinetic Properties of Coumarin–Hydroxybenzohydrazide Hybrids |
| title_sort | radical scavenging activity and pharmacokinetic properties of coumarin hydroxybenzohydrazide hybrids |
| topic | radical scavenging antioxidants coumarins DFT pharmacokinetics |
| url | https://www.mdpi.com/1422-0067/23/1/490 |
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