Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds
Nowadays, oxidative cell damage is one of the common features of cancer and Alzheimer’s disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/1/139 |
| _version_ | 1797446860402589696 |
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| author | Nora Astrain-Redin Irene Talavera Esther Moreno María J. Ramírez Nuria Martínez-Sáez Ignacio Encío Arun K. Sharma Carmen Sanmartín Daniel Plano |
| author_facet | Nora Astrain-Redin Irene Talavera Esther Moreno María J. Ramírez Nuria Martínez-Sáez Ignacio Encío Arun K. Sharma Carmen Sanmartín Daniel Plano |
| author_sort | Nora Astrain-Redin |
| collection | DOAJ |
| description | Nowadays, oxidative cell damage is one of the common features of cancer and Alzheimer’s disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total of 39 Se-derivatives were synthesized, purified, and spectroscopically characterized by NMR. Antioxidant ability was tested using the DPPH assay, while antiproliferative activity was screened in breast, lung, prostate, and colorectal cancer cell lines. In addition, as a first approach to evaluate their potential anti-Alzheimer activity, the in vitro acetylcholinesterase inhibition (AChEI) was tested. Regarding antioxidant properties, compound <b>13a</b> showed concentration- and time-dependent radical scavenging activity. Additionally, compounds <b>14a</b> and <b>17a</b> showed high activity in the melanoma and ovarian cancer cell lines, with LD<sub>50</sub> values below 9.2 µM. Interestingly, in the AChEI test, compound <b>14a</b> showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10<sup>−6</sup> cm/s). Molecular dynamics simulations of the aspirin derivatives (<b>14a</b> and <b>14b</b>) confirm the importance of the allylic group instead of the propargyl one. Altogether, it is concluded that some of these newly synthesized Se-derivatives, such as <b>14a</b>, might become very promising candidates to treat both cancer and AD. |
| first_indexed | 2024-03-09T13:46:42Z |
| format | Article |
| id | doaj.art-e910cf08000144dcbd9ce1a4b4028c86 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T13:46:42Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e910cf08000144dcbd9ce1a4b4028c862023-11-30T20:58:51ZengMDPI AGAntioxidants2076-39212023-01-0112113910.3390/antiox12010139Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual CompoundsNora Astrain-Redin0Irene Talavera1Esther Moreno2María J. Ramírez3Nuria Martínez-Sáez4Ignacio Encío5Arun K. Sharma6Carmen Sanmartín7Daniel Plano8Departamento de Tecnología y Química Farmacéuticas, Facultad de Farmacia y Nutrición, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainDepartamento de Tecnología y Química Farmacéuticas, Facultad de Farmacia y Nutrición, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainDepartamento de Tecnología y Química Farmacéuticas, Facultad de Farmacia y Nutrición, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainDepartamento de Farmacología y Toxicología, Facultad de Farmacia y Nutrición, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainDepartamento de Tecnología y Química Farmacéuticas, Facultad de Farmacia y Nutrición, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainDepartamento de Ciencias de la Salud, Universidad Pública de Navarra, Avda. Barañain s/n, E-31008 Pamplona, SpainDepartment of Pharmacology, Penn State Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USADepartamento de Tecnología y Química Farmacéuticas, Facultad de Farmacia y Nutrición, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainDepartamento de Tecnología y Química Farmacéuticas, Facultad de Farmacia y Nutrición, Universidad de Navarra, Irunlarrea 1, E-31008 Pamplona, SpainNowadays, oxidative cell damage is one of the common features of cancer and Alzheimer’s disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total of 39 Se-derivatives were synthesized, purified, and spectroscopically characterized by NMR. Antioxidant ability was tested using the DPPH assay, while antiproliferative activity was screened in breast, lung, prostate, and colorectal cancer cell lines. In addition, as a first approach to evaluate their potential anti-Alzheimer activity, the in vitro acetylcholinesterase inhibition (AChEI) was tested. Regarding antioxidant properties, compound <b>13a</b> showed concentration- and time-dependent radical scavenging activity. Additionally, compounds <b>14a</b> and <b>17a</b> showed high activity in the melanoma and ovarian cancer cell lines, with LD<sub>50</sub> values below 9.2 µM. Interestingly, in the AChEI test, compound <b>14a</b> showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10<sup>−6</sup> cm/s). Molecular dynamics simulations of the aspirin derivatives (<b>14a</b> and <b>14b</b>) confirm the importance of the allylic group instead of the propargyl one. Altogether, it is concluded that some of these newly synthesized Se-derivatives, such as <b>14a</b>, might become very promising candidates to treat both cancer and AD.https://www.mdpi.com/2076-3921/12/1/139canceracetylcholinesteraseseleniumNSAIDsallylpropargyl |
| spellingShingle | Nora Astrain-Redin Irene Talavera Esther Moreno María J. Ramírez Nuria Martínez-Sáez Ignacio Encío Arun K. Sharma Carmen Sanmartín Daniel Plano Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds Antioxidants cancer acetylcholinesterase selenium NSAIDs allyl propargyl |
| title | Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds |
| title_full | Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds |
| title_fullStr | Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds |
| title_full_unstemmed | Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds |
| title_short | Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds |
| title_sort | seleno analogs of scaffolds resembling natural products a novel warhead toward dual compounds |
| topic | cancer acetylcholinesterase selenium NSAIDs allyl propargyl |
| url | https://www.mdpi.com/2076-3921/12/1/139 |
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