Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents
A series of 30 novel <i>N</i>,<i>N</i> disubstituted selenoureas were synthesized, characterized, and their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/5/777 |
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| author | Gorka Calvo-Martín Daniel Plano Ignacio Encío Carmen Sanmartín |
| author_facet | Gorka Calvo-Martín Daniel Plano Ignacio Encío Carmen Sanmartín |
| author_sort | Gorka Calvo-Martín |
| collection | DOAJ |
| description | A series of 30 novel <i>N</i>,<i>N</i> disubstituted selenoureas were synthesized, characterized, and their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cytotoxic activity was tested in vitro in a panel of three different cancer (breast, lung and colon) and two normal cell lines. Each selenourea entity contains a para-substituted phenyl ring with different electron-withdrawing and electron-donating groups, and different aliphatic and aromatic nuclei. All of the synthesized selenoureas present antioxidant capacity at high concentrations in the DPPH assay, and three of them (<b>2b</b>, <b>2c</b> and <b>2d</b>) showed greater radical scavenging capacity than ascorbic acid at lower concentrations. These results were confirmed by the ABTS assay, where these novel selenoureas present even higher antioxidant capacity than the reference compound Trolox. On the other hand, 10 selenoureas present IC<sub>50</sub> values below 10 µM in at least one cancer cell line, resulting in the adamantyl nucleus (<b>6a</b>–<b>6e</b>), the most interesting in terms of activity and selectivity. Outstanding results were found for selenourea <b>6c</b>, tested in the NCI60 cell line panel and showing an average GI<sub>50</sub> of 1.49 µM for the 60 cell lines, and LC<sub>50</sub> values ranging from 9.33 µM to 4.27 µM against 10 of these cancer cell lines. To gain insight into its anticancer activity mechanism, we investigated the cell cycle progression of the promising compound <b>6c</b>, as well as the type of programmed-cell death in a colon cancer cell line it provokes (HT-29). Compound <b>6c</b> provoked S phase cell cycle arrest and the induction of cell death was independent of caspase activation, suggesting autophagy, though this assertion requires additional studies. Overall, we envision that this compound can be further developed for the potential treatment of colon cancer. |
| first_indexed | 2024-03-10T11:26:22Z |
| format | Article |
| id | doaj.art-f0d45ab775944c2898ce42699178ce79 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T11:26:22Z |
| publishDate | 2021-05-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-f0d45ab775944c2898ce42699178ce792023-11-21T19:41:26ZengMDPI AGAntioxidants2076-39212021-05-0110577710.3390/antiox10050777Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic AgentsGorka Calvo-Martín0Daniel Plano1Ignacio Encío2Carmen Sanmartín3Departamento de Tecnología y Química Farmacéuticas, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainDepartamento de Tecnología y Química Farmacéuticas, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea, 3, E-31008 Pamplona, SpainDepartamento de Tecnología y Química Farmacéuticas, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainA series of 30 novel <i>N</i>,<i>N</i> disubstituted selenoureas were synthesized, characterized, and their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cytotoxic activity was tested in vitro in a panel of three different cancer (breast, lung and colon) and two normal cell lines. Each selenourea entity contains a para-substituted phenyl ring with different electron-withdrawing and electron-donating groups, and different aliphatic and aromatic nuclei. All of the synthesized selenoureas present antioxidant capacity at high concentrations in the DPPH assay, and three of them (<b>2b</b>, <b>2c</b> and <b>2d</b>) showed greater radical scavenging capacity than ascorbic acid at lower concentrations. These results were confirmed by the ABTS assay, where these novel selenoureas present even higher antioxidant capacity than the reference compound Trolox. On the other hand, 10 selenoureas present IC<sub>50</sub> values below 10 µM in at least one cancer cell line, resulting in the adamantyl nucleus (<b>6a</b>–<b>6e</b>), the most interesting in terms of activity and selectivity. Outstanding results were found for selenourea <b>6c</b>, tested in the NCI60 cell line panel and showing an average GI<sub>50</sub> of 1.49 µM for the 60 cell lines, and LC<sub>50</sub> values ranging from 9.33 µM to 4.27 µM against 10 of these cancer cell lines. To gain insight into its anticancer activity mechanism, we investigated the cell cycle progression of the promising compound <b>6c</b>, as well as the type of programmed-cell death in a colon cancer cell line it provokes (HT-29). Compound <b>6c</b> provoked S phase cell cycle arrest and the induction of cell death was independent of caspase activation, suggesting autophagy, though this assertion requires additional studies. Overall, we envision that this compound can be further developed for the potential treatment of colon cancer.https://www.mdpi.com/2076-3921/10/5/777selenoureasantioxidantcytotoxicityradical scavengingselenium |
| spellingShingle | Gorka Calvo-Martín Daniel Plano Ignacio Encío Carmen Sanmartín Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents Antioxidants selenoureas antioxidant cytotoxicity radical scavenging selenium |
| title | Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents |
| title_full | Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents |
| title_fullStr | Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents |
| title_full_unstemmed | Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents |
| title_short | Novel <i>N</i>,<i>N</i>′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents |
| title_sort | novel i n i i n i disubstituted selenoureas as potential antioxidant and cytotoxic agents |
| topic | selenoureas antioxidant cytotoxicity radical scavenging selenium |
| url | https://www.mdpi.com/2076-3921/10/5/777 |
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