Triazole-based estradiol dimers prepared via CuAAC from 17α-ethinyl estradiol with five-atom linkers causing G2/M arrest and tubulin inhibition.
| Autor: | Jurášek M; Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic., Řehulka J; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic., Hrubá L; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic., Ivanová A; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic., Gurská S; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic., Mokshyna O; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic., Trousil P; Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic., Huml L; Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic., Polishchuk P; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic., Hajdúch M; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic., Drašar PB; Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic., Džubák P; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, 779 00 Olomouc, Czech Republic. Electronic address: petr.dzubak@upol.cz. |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic chemistry [Bioorg Chem] 2023 Feb; Vol. 131, pp. 106334. Date of Electronic Publication: 2022 Dec 23. |
| DOI: | 10.1016/j.bioorg.2022.106334 |
| Abstrakt: | Microtubule dynamic is exceptionally sensitive to modulation by small-molecule ligands. Our previous work presented the preparation of microtubule-targeting estradiol dimer (ED) with anticancer activity. In the present study, we explore the effect of selected linkers on the biological activity of the dimer. The linkers were designed as five-atom chains with carbon, nitrogen or oxygen in their centre. In addition, the central nitrogen was modified by a benzyl group with hydroxy or methoxy substituents and one derivative possessed an extended linker length. Thirteen new dimers were subjected to cytotoxicity assay and cell cycle profiling. Dimers containing linker with benzyl moiety substituted with one or more methoxy groups and longer branched ones were found inactive, whereas other structures had comparable efficacy as the original ED (e.g. D1 with IC Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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