Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-ones
Quinazolinones represent an important scaffold in medicinal chemistry with diverse biological activities. Here, two series of 2-substituted quinazolin-4(3<i>H</i>)-ones were synthesized and evaluated for their antioxidant properties using three different methods, namely DPPH, ABTS and TE...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/21/6585 |
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| author | Janez Mravljak Lara Slavec Martina Hrast Matej Sova |
| author_facet | Janez Mravljak Lara Slavec Martina Hrast Matej Sova |
| author_sort | Janez Mravljak |
| collection | DOAJ |
| description | Quinazolinones represent an important scaffold in medicinal chemistry with diverse biological activities. Here, two series of 2-substituted quinazolin-4(3<i>H</i>)-ones were synthesized and evaluated for their antioxidant properties using three different methods, namely DPPH, ABTS and TEAC<sub>CUPRAC</sub>, to obtain key information about the structure–antioxidant activity relationships of a diverse set of substituents at position 2 of the main quinazolinone scaffold. Regarding the antioxidant activity, ABTS and TEAC<sub>CUPRAC</sub> assays were more sensitive and gave more reliable results than the DPPH assay. To obtain antioxidant activity of 2-phenylquinazolin-4(3<i>H</i>)-one, the presence of at least one hydroxyl group in addition to the methoxy substituent or the second hydroxyl on the phenyl ring in the ortho or para positions is required. An additional ethylene linker between quinazolinone ring and phenolic substituent, present in the second series (compounds <b>25a</b> and <b>25b</b>), leads to increased antioxidant activity. Furthermore, in addition to antioxidant activity, the derivatives with two hydroxyl groups in the ortho position on the phenyl ring exhibited metal-chelating properties. Our study represents a successful use of three different antioxidant activity evaluation methods to define 2-(2,3-dihydroxyphenyl)quinazolin-4(3<i>H</i>)-one <b>21e</b> as a potent antioxidant with promising metal-chelating properties. |
| first_indexed | 2024-03-10T05:56:18Z |
| format | Article |
| id | doaj.art-e73e428c490f4cc191f015f12b1a5666 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:56:18Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e73e428c490f4cc191f015f12b1a56662023-11-22T21:23:33ZengMDPI AGMolecules1420-30492021-10-012621658510.3390/molecules26216585Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-onesJanez Mravljak0Lara Slavec1Martina Hrast2Matej Sova3Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, SloveniaFaculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, SloveniaFaculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, SloveniaFaculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, SloveniaQuinazolinones represent an important scaffold in medicinal chemistry with diverse biological activities. Here, two series of 2-substituted quinazolin-4(3<i>H</i>)-ones were synthesized and evaluated for their antioxidant properties using three different methods, namely DPPH, ABTS and TEAC<sub>CUPRAC</sub>, to obtain key information about the structure–antioxidant activity relationships of a diverse set of substituents at position 2 of the main quinazolinone scaffold. Regarding the antioxidant activity, ABTS and TEAC<sub>CUPRAC</sub> assays were more sensitive and gave more reliable results than the DPPH assay. To obtain antioxidant activity of 2-phenylquinazolin-4(3<i>H</i>)-one, the presence of at least one hydroxyl group in addition to the methoxy substituent or the second hydroxyl on the phenyl ring in the ortho or para positions is required. An additional ethylene linker between quinazolinone ring and phenolic substituent, present in the second series (compounds <b>25a</b> and <b>25b</b>), leads to increased antioxidant activity. Furthermore, in addition to antioxidant activity, the derivatives with two hydroxyl groups in the ortho position on the phenyl ring exhibited metal-chelating properties. Our study represents a successful use of three different antioxidant activity evaluation methods to define 2-(2,3-dihydroxyphenyl)quinazolin-4(3<i>H</i>)-one <b>21e</b> as a potent antioxidant with promising metal-chelating properties.https://www.mdpi.com/1420-3049/26/21/6585quinazolinonesynthesisantioxidantDPPHABTSCUPRAC |
| spellingShingle | Janez Mravljak Lara Slavec Martina Hrast Matej Sova Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-ones Molecules quinazolinone synthesis antioxidant DPPH ABTS CUPRAC |
| title | Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-ones |
| title_full | Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-ones |
| title_fullStr | Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-ones |
| title_full_unstemmed | Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-ones |
| title_short | Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(<i>3H</i>)-ones |
| title_sort | synthesis and evaluation of antioxidant properties of 2 substituted quinazolin 4 i 3h i ones |
| topic | quinazolinone synthesis antioxidant DPPH ABTS CUPRAC |
| url | https://www.mdpi.com/1420-3049/26/21/6585 |
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