An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status
In this study, green synthesis of two derivatives of coumarin–hydroxybenzohydrazide, (<i>E</i>)-2,4-dioxo-3-(1-(2-(2,3,4-trihydroxybenzoyl)hydrazyl)ethylidene)-chroman-7-yl acetate (<b>C–HB<sub>1</sub></b>), and (<i>E</i>)-2,4-dioxo-3-(1-(2-(3,4,5-trih...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/12/2070 |
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| author | Edina H. Avdović Žiko Milanović Dušica Simijonović Marko Antonijević Milena Milutinović Danijela Nikodijević Nenad Filipović Zoran Marković Radiša Vojinović |
| author_facet | Edina H. Avdović Žiko Milanović Dušica Simijonović Marko Antonijević Milena Milutinović Danijela Nikodijević Nenad Filipović Zoran Marković Radiša Vojinović |
| author_sort | Edina H. Avdović |
| collection | DOAJ |
| description | In this study, green synthesis of two derivatives of coumarin–hydroxybenzohydrazide, (<i>E</i>)-2,4-dioxo-3-(1-(2-(2,3,4-trihydroxybenzoyl)hydrazyl)ethylidene)-chroman-7-yl acetate (<b>C–HB<sub>1</sub></b>), and (<i>E</i>)-2,4-dioxo-3-(1-(2-(3,4,5-trihydroxybenzoyl)hydrazyl)ethylidene)chroman-7-yl acetate (<b>C–HB<sub>2</sub></b>) is reported. Using vinegar and ethanol as a catalyst and solvent, the reactions were carried out between 3-acetyl-4-hydroxy-coumarin acetate and corresponding trihydroxybenzoyl hydrazide. The antioxidant potential of these compounds was investigated using the DPPH and ABTS assays, as well as the FRAP test. The obtained results reveal that even at very low concentrations, these compounds show excellent radical scavenging potential. The IC<sub>50</sub> values for C-HB<sub>1</sub> and C-HB<sub>2</sub> in relation to the DPPH radical are 6.4 and 2.5 μM, respectively, while they are 4.5 and 2.0 μM in relation to the ABTS radical. These compounds have antioxidant activity that is comparable to well-known antioxidants such as gallic acid, NDGA, and trolox. These results are in good correlation with theoretical parameters describing these reactions. Moreover, it was found that inhibition of DPPH<sup>●</sup> follows HAT, while inactivation of ABTS<sup>+●</sup> follows SET-PT and HAT mechanisms. Additionally, coumarin–hydroxybenzohydrazide derivatives induced moderate cytotoxic activity and show significant potential to modulate redox status in HCT-116 colorectal cancer cells. The cytotoxicity was achieved via their prooxidative activity and ability to induce oxidative stress in cancer cells by increasing O<sub>2</sub>˙<sup>−</sup> concentrations, indicated by increased MDA and GSH levels. Thus, ROS manipulation can be a potential target for cancer therapies by coumarins, as cancer cells possess an altered redox balance in comparison to normal cells. According to the ADMET analysis, the compounds investigated show good pharmacokinetic and toxicological profiles similar to vitamin C and gallic acid, which makes them good candidates for application in various fields of industry and medicine. |
| first_indexed | 2024-03-08T21:02:54Z |
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| id | doaj.art-bfa890277ccb4fa39cae7b4fd3252587 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T21:02:54Z |
| publishDate | 2023-12-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-bfa890277ccb4fa39cae7b4fd32525872023-12-22T13:48:25ZengMDPI AGAntioxidants2076-39212023-12-011212207010.3390/antiox12122070An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox StatusEdina H. Avdović0Žiko Milanović1Dušica Simijonović2Marko Antonijević3Milena Milutinović4Danijela Nikodijević5Nenad Filipović6Zoran Marković7Radiša Vojinović8Department 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 Biology and Ecology, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, SerbiaDepartment of Biology and Ecology, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, SerbiaFaculty of Engineering, University of Kragujevac, Sestre Janjic 6, 34000 Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaFaculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, SerbiaIn this study, green synthesis of two derivatives of coumarin–hydroxybenzohydrazide, (<i>E</i>)-2,4-dioxo-3-(1-(2-(2,3,4-trihydroxybenzoyl)hydrazyl)ethylidene)-chroman-7-yl acetate (<b>C–HB<sub>1</sub></b>), and (<i>E</i>)-2,4-dioxo-3-(1-(2-(3,4,5-trihydroxybenzoyl)hydrazyl)ethylidene)chroman-7-yl acetate (<b>C–HB<sub>2</sub></b>) is reported. Using vinegar and ethanol as a catalyst and solvent, the reactions were carried out between 3-acetyl-4-hydroxy-coumarin acetate and corresponding trihydroxybenzoyl hydrazide. The antioxidant potential of these compounds was investigated using the DPPH and ABTS assays, as well as the FRAP test. The obtained results reveal that even at very low concentrations, these compounds show excellent radical scavenging potential. The IC<sub>50</sub> values for C-HB<sub>1</sub> and C-HB<sub>2</sub> in relation to the DPPH radical are 6.4 and 2.5 μM, respectively, while they are 4.5 and 2.0 μM in relation to the ABTS radical. These compounds have antioxidant activity that is comparable to well-known antioxidants such as gallic acid, NDGA, and trolox. These results are in good correlation with theoretical parameters describing these reactions. Moreover, it was found that inhibition of DPPH<sup>●</sup> follows HAT, while inactivation of ABTS<sup>+●</sup> follows SET-PT and HAT mechanisms. Additionally, coumarin–hydroxybenzohydrazide derivatives induced moderate cytotoxic activity and show significant potential to modulate redox status in HCT-116 colorectal cancer cells. The cytotoxicity was achieved via their prooxidative activity and ability to induce oxidative stress in cancer cells by increasing O<sub>2</sub>˙<sup>−</sup> concentrations, indicated by increased MDA and GSH levels. Thus, ROS manipulation can be a potential target for cancer therapies by coumarins, as cancer cells possess an altered redox balance in comparison to normal cells. According to the ADMET analysis, the compounds investigated show good pharmacokinetic and toxicological profiles similar to vitamin C and gallic acid, which makes them good candidates for application in various fields of industry and medicine.https://www.mdpi.com/2076-3921/12/12/2070coumarinsgreen synthesisantioxidant activityredox statuscancer therapy |
| spellingShingle | Edina H. Avdović Žiko Milanović Dušica Simijonović Marko Antonijević Milena Milutinović Danijela Nikodijević Nenad Filipović Zoran Marković Radiša Vojinović An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status Antioxidants coumarins green synthesis antioxidant activity redox status cancer therapy |
| title | An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status |
| title_full | An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status |
| title_fullStr | An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status |
| title_full_unstemmed | An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status |
| title_short | An Effective, Green Synthesis Procedure for Obtaining Coumarin–Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status |
| title_sort | effective green synthesis procedure for obtaining coumarin hydroxybenzohydrazide derivatives and assessment of their antioxidant activity and redox status |
| topic | coumarins green synthesis antioxidant activity redox status cancer therapy |
| url | https://www.mdpi.com/2076-3921/12/12/2070 |
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