Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives
2- or 4-Substituted 3-N-benzyltriazolylmethyl-13α-oestrone derivatives were synthesised via bromination of ring A and subsequent microwave-assisted, Pd-catalysed C(sp2)–P couplings. The antiproliferative activities of the newly synthesised brominated and phosphonated compounds against a panel of hum...
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Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2020.1838500 |
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doaj-c0787edc2150496687f0aa73c57bbf212020-11-25T04:02:35ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-01361586710.1080/14756366.2020.18385001838500Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivativesRebeka Jójárt0Seyyed Ashkan Senobar Tahaei1Péter Trungel-Nagy2Zoltán Kele3Renáta Minorics4Gábor Paragi5István Zupkó6Erzsébet Mernyák7Department of Organic Chemistry, University of SzegedDepartment of Pharmacodynamics and Biopharmacy, University of SzegedDepartment of Organic Chemistry, University of SzegedDepartment of Medicinal Chemistry, University of SzegedDepartment of Pharmacodynamics and Biopharmacy, University of SzegedMTA-SZTE Biomimetic Systems Research Group, University of SzegedDepartment of Pharmacodynamics and Biopharmacy, University of SzegedDepartment of Organic Chemistry, University of Szeged2- or 4-Substituted 3-N-benzyltriazolylmethyl-13α-oestrone derivatives were synthesised via bromination of ring A and subsequent microwave-assisted, Pd-catalysed C(sp2)–P couplings. The antiproliferative activities of the newly synthesised brominated and phosphonated compounds against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231) were investigated by means of MTT assays. The most potent compound, the 3-N-benzyltriazolylmethyl-4-bromo-13α-oestrone derivative exerted substantial selective cell growth-inhibitory activity against A2780 cell line with a submicromolar IC50 value. Computational calculations reveal strong interactions of the 4-bromo derivative with both colchicine and taxoid binding sites of tubulin. Disturbance of tubulin function has been confirmed by photometric polymerisation assay.http://dx.doi.org/10.1080/14756366.2020.1838500hirao reactionazide–alkyne cycloadditionantiproliferative effecttubulin polymerisationmolecular dynamics |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Rebeka Jójárt Seyyed Ashkan Senobar Tahaei Péter Trungel-Nagy Zoltán Kele Renáta Minorics Gábor Paragi István Zupkó Erzsébet Mernyák |
| spellingShingle |
Rebeka Jójárt Seyyed Ashkan Senobar Tahaei Péter Trungel-Nagy Zoltán Kele Renáta Minorics Gábor Paragi István Zupkó Erzsébet Mernyák Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives Journal of Enzyme Inhibition and Medicinal Chemistry hirao reaction azide–alkyne cycloaddition antiproliferative effect tubulin polymerisation molecular dynamics |
| author_facet |
Rebeka Jójárt Seyyed Ashkan Senobar Tahaei Péter Trungel-Nagy Zoltán Kele Renáta Minorics Gábor Paragi István Zupkó Erzsébet Mernyák |
| author_sort |
Rebeka Jójárt |
| title |
Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives |
| title_short |
Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives |
| title_full |
Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives |
| title_fullStr |
Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives |
| title_full_unstemmed |
Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives |
| title_sort |
synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(n-benzyltriazolylmethyl)-13α-oestrone derivatives |
| publisher |
Taylor & Francis Group |
| series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
| issn |
1475-6366 1475-6374 |
| publishDate |
2021-01-01 |
| description |
2- or 4-Substituted 3-N-benzyltriazolylmethyl-13α-oestrone derivatives were synthesised via bromination of ring A and subsequent microwave-assisted, Pd-catalysed C(sp2)–P couplings. The antiproliferative activities of the newly synthesised brominated and phosphonated compounds against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231) were investigated by means of MTT assays. The most potent compound, the 3-N-benzyltriazolylmethyl-4-bromo-13α-oestrone derivative exerted substantial selective cell growth-inhibitory activity against A2780 cell line with a submicromolar IC50 value. Computational calculations reveal strong interactions of the 4-bromo derivative with both colchicine and taxoid binding sites of tubulin. Disturbance of tubulin function has been confirmed by photometric polymerisation assay. |
| topic |
hirao reaction azide–alkyne cycloaddition antiproliferative effect tubulin polymerisation molecular dynamics |
| url |
http://dx.doi.org/10.1080/14756366.2020.1838500 |
| work_keys_str_mv |
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