Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers
Novel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan–Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethe...
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/1196 |
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| author | Édua Kovács Hazhmat Ali Renáta Minorics Péter Traj Vivien Resch Gábor Paragi Bella Bruszel István Zupkó Erzsébet Mernyák |
| author_facet | Édua Kovács Hazhmat Ali Renáta Minorics Péter Traj Vivien Resch Gábor Paragi Bella Bruszel István Zupkó Erzsébet Mernyák |
| author_sort | Édua Kovács |
| collection | DOAJ |
| description | Novel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan–Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethers against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231, HeLa, SiHa) were investigated by means of MTT assays. The quinoline derivative displayed substantial antiproliferative activity against MCF-7 and HeLa cell lines with low micromolar IC<sub>50</sub> values. Disturbance of tubulin polymerization has been confirmed by microplate-based photometric assay. Computational calculations reveal significant interactions of the quinoline derivative with the taxoid binding site of tubulin. |
| first_indexed | 2024-03-11T09:33:35Z |
| format | Article |
| id | doaj.art-a3ec26607c184587b7bd532a93501e55 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:33:35Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a3ec26607c184587b7bd532a93501e552023-11-16T17:29:00ZengMDPI AGMolecules1420-30492023-01-01283119610.3390/molecules28031196Synthesis and Antiproliferative Activity of Steroidal Diaryl EthersÉdua Kovács0Hazhmat Ali1Renáta Minorics2Péter Traj3Vivien Resch4Gábor Paragi5Bella Bruszel6István Zupkó7Erzsébet Mernyák8Department of Organic Chemistry, University of Szeged, H-6720 Szeged, HungaryInstitute of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, HungaryInstitute of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, HungaryDepartment of Organic Chemistry, University of Szeged, H-6720 Szeged, HungaryDepartment of Medicinal Chemistry, University of Szeged, H-6720 Szeged, HungaryDepartment of Medicinal Chemistry, University of Szeged, H-6720 Szeged, HungaryDepartment of Medicinal Chemistry, University of Szeged, H-6720 Szeged, HungaryInstitute of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, HungaryDepartment of Organic Chemistry, University of Szeged, H-6720 Szeged, HungaryNovel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan–Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethers against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231, HeLa, SiHa) were investigated by means of MTT assays. The quinoline derivative displayed substantial antiproliferative activity against MCF-7 and HeLa cell lines with low micromolar IC<sub>50</sub> values. Disturbance of tubulin polymerization has been confirmed by microplate-based photometric assay. Computational calculations reveal significant interactions of the quinoline derivative with the taxoid binding site of tubulin.https://www.mdpi.com/1420-3049/28/3/1196Chan–Lam reactiondiaryl ether13α-estroneantiproliferative effecttubulin polymerizationmolecular dynamics |
| spellingShingle | Édua Kovács Hazhmat Ali Renáta Minorics Péter Traj Vivien Resch Gábor Paragi Bella Bruszel István Zupkó Erzsébet Mernyák Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers Molecules Chan–Lam reaction diaryl ether 13α-estrone antiproliferative effect tubulin polymerization molecular dynamics |
| title | Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers |
| title_full | Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers |
| title_fullStr | Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers |
| title_full_unstemmed | Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers |
| title_short | Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers |
| title_sort | synthesis and antiproliferative activity of steroidal diaryl ethers |
| topic | Chan–Lam reaction diaryl ether 13α-estrone antiproliferative effect tubulin polymerization molecular dynamics |
| url | https://www.mdpi.com/1420-3049/28/3/1196 |
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