Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones
Herein, we report the synthesis and antioxidant capacity of twelve novel 1,2,3-triazole-containing nitrones such as <i>N</i>-(2-(4-aryl-1<i>H</i>-1,2,3-triazol-1-yl)ethylidene)methanamine oxides <b>8a</b>–<b>f</b> and <i>N</i>-(2-(4-aryl)-1...
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MDPI AG
2022-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/1/36 |
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| author | Dimitra Hadjipavlou-Litina Iwona E. Głowacka José Marco-Contelles Dorota G. Piotrowska |
| author_facet | Dimitra Hadjipavlou-Litina Iwona E. Głowacka José Marco-Contelles Dorota G. Piotrowska |
| author_sort | Dimitra Hadjipavlou-Litina |
| collection | DOAJ |
| description | Herein, we report the synthesis and antioxidant capacity of twelve novel 1,2,3-triazole-containing nitrones such as <i>N</i>-(2-(4-aryl-1<i>H</i>-1,2,3-triazol-1-yl)ethylidene)methanamine oxides <b>8a</b>–<b>f</b> and <i>N</i>-(2-(4-aryl)-1<i>H</i>-1,2,3-triazol-1-yl)ethylidene)-2-methylpropan-2-amine oxides <b>9a</b>–<b>f</b>, bearing an <i>N</i>-methyl, and an <i>N-t</i>-butyl substituent, respectively, at the nitrogen of the nitrone motif. Nitrones <b>8</b> and <b>9</b> were studied with regard to their antioxidant ability, as well as their ability to inhibit soybean lypoxygenase (LOX), and their in vitro antioxidant activity. For this, we used three different antioxidant assays, such as that featuring the interaction with the water-soluble azo compound AAPH for the inhibition of lipid peroxidation (LP), the competition with the DMSO for scavenging hydroxyl radicals, and the ABTS<sup>•+</sup>–decolorization assay. <i>t</i>-Butyl nitrone <b>9e</b>, bearing the 2,4-difluorophenyl motif, showed a strong LP inhibitory effect (100%), close to the reference compound Trolox (93%), being the most potent LP inhibitor (LPi) of the whole series of tested nitrones. Nitrones <b>9d</b>, <b>9e</b> and <b>9f</b>, bearing the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, were almost equipotent, and the most potent hydroxyl radical scavengers (~100%), more potent than Trolox (88%), were used as a reference compound. Regarding the LOX inhibition, the most potent inhibitor was the <i>t</i>-butyl substituted nitrone <b>9f</b> (27 μM), bearing the 4-fluoro-3-methylphenyl motif, being 60-fold less potent than NDGA (0.45 μM), which was used as the standard in this test. The results from the antioxidant determination in the ABTS radical cation (ABTS<sup>•+</sup>) decolorization assay were not significant. <i>N</i>-Methyl nitrone <b>8f</b>, bearing the 4-fluoro-3-methylphenyl motif, was the only promising representative, with a value of 34.3%, followed by nitrone <b>9f</b> (16%). From the antioxidant analyses, we have identified <i>N</i>-(2-(4-(4-fluoro-3-methylphenyl)-1<i>H</i>-1,2,3-triazol-1-yl)ethylidene)-2-methylpropan-2-amine oxide (<b>9f</b>), bearing <i>t</i>-butyl and 4-fluoro-3-methylphenyl motifs in its structure, as the most balanced and potent antioxidant agent among the tested nitrones, as it was the most potent LOX inhibitor (27 μM), an extremely efficient and potent hydroxyl radical scavenger (99.9%), as well as one of the most potent LPi (87%) and ABTS<sup>•+</sup> scavengers (16%). |
| first_indexed | 2024-03-09T13:47:13Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T13:47:13Z |
| publishDate | 2022-12-01 |
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| series | Antioxidants |
| spelling | doaj.art-71b8d4f1c1ed4ac9af48c432f07963cd2023-11-30T20:57:26ZengMDPI AGAntioxidants2076-39212022-12-011213610.3390/antiox12010036Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing NitronesDimitra Hadjipavlou-Litina0Iwona E. Głowacka1José Marco-Contelles2Dorota G. Piotrowska3Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceBioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, PolandLaboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006 Madrid, SpainBioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, PolandHerein, we report the synthesis and antioxidant capacity of twelve novel 1,2,3-triazole-containing nitrones such as <i>N</i>-(2-(4-aryl-1<i>H</i>-1,2,3-triazol-1-yl)ethylidene)methanamine oxides <b>8a</b>–<b>f</b> and <i>N</i>-(2-(4-aryl)-1<i>H</i>-1,2,3-triazol-1-yl)ethylidene)-2-methylpropan-2-amine oxides <b>9a</b>–<b>f</b>, bearing an <i>N</i>-methyl, and an <i>N-t</i>-butyl substituent, respectively, at the nitrogen of the nitrone motif. Nitrones <b>8</b> and <b>9</b> were studied with regard to their antioxidant ability, as well as their ability to inhibit soybean lypoxygenase (LOX), and their in vitro antioxidant activity. For this, we used three different antioxidant assays, such as that featuring the interaction with the water-soluble azo compound AAPH for the inhibition of lipid peroxidation (LP), the competition with the DMSO for scavenging hydroxyl radicals, and the ABTS<sup>•+</sup>–decolorization assay. <i>t</i>-Butyl nitrone <b>9e</b>, bearing the 2,4-difluorophenyl motif, showed a strong LP inhibitory effect (100%), close to the reference compound Trolox (93%), being the most potent LP inhibitor (LPi) of the whole series of tested nitrones. Nitrones <b>9d</b>, <b>9e</b> and <b>9f</b>, bearing the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, were almost equipotent, and the most potent hydroxyl radical scavengers (~100%), more potent than Trolox (88%), were used as a reference compound. Regarding the LOX inhibition, the most potent inhibitor was the <i>t</i>-butyl substituted nitrone <b>9f</b> (27 μM), bearing the 4-fluoro-3-methylphenyl motif, being 60-fold less potent than NDGA (0.45 μM), which was used as the standard in this test. The results from the antioxidant determination in the ABTS radical cation (ABTS<sup>•+</sup>) decolorization assay were not significant. <i>N</i>-Methyl nitrone <b>8f</b>, bearing the 4-fluoro-3-methylphenyl motif, was the only promising representative, with a value of 34.3%, followed by nitrone <b>9f</b> (16%). From the antioxidant analyses, we have identified <i>N</i>-(2-(4-(4-fluoro-3-methylphenyl)-1<i>H</i>-1,2,3-triazol-1-yl)ethylidene)-2-methylpropan-2-amine oxide (<b>9f</b>), bearing <i>t</i>-butyl and 4-fluoro-3-methylphenyl motifs in its structure, as the most balanced and potent antioxidant agent among the tested nitrones, as it was the most potent LOX inhibitor (27 μM), an extremely efficient and potent hydroxyl radical scavenger (99.9%), as well as one of the most potent LPi (87%) and ABTS<sup>•+</sup> scavengers (16%).https://www.mdpi.com/2076-3921/12/1/36antioxidantsoxidative stress1,2,3-Triazole-containing nitrones |
| spellingShingle | Dimitra Hadjipavlou-Litina Iwona E. Głowacka José Marco-Contelles Dorota G. Piotrowska Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones Antioxidants antioxidants oxidative stress 1,2,3-Triazole-containing nitrones |
| title | Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones |
| title_full | Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones |
| title_fullStr | Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones |
| title_full_unstemmed | Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones |
| title_short | Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones |
| title_sort | synthesis and antioxidant properties of novel 1 2 3 triazole containing nitrones |
| topic | antioxidants oxidative stress 1,2,3-Triazole-containing nitrones |
| url | https://www.mdpi.com/2076-3921/12/1/36 |
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