Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates
2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC). For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The...
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MDPI AG
2016-09-01
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| author | Brigitta Bodnár Erzsébet Mernyák János Wölfling Gyula Schneider Bianka Edina Herman Mihály Szécsi Izabella Sinka István Zupkó Zoltán Kupihár Lajos Kovács |
| author_facet | Brigitta Bodnár Erzsébet Mernyák János Wölfling Gyula Schneider Bianka Edina Herman Mihály Szécsi Izabella Sinka István Zupkó Zoltán Kupihár Lajos Kovács |
| author_sort | Brigitta Bodnár |
| collection | DOAJ |
| description | 2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC). For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3′-hydroxy groups of the nucleosides were protected by acetyl groups and the 5′-hydroxy groups were modified by the tosyl–azide exchange method. The commonly used conditions for click reaction between the protected-5′-azidonucleosides and the steroid alkyne was slightly modified by using 1.5 equivalent of Cu(I) catalyst. All the prepared conjugates were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7 and A2780) and the potential inhibitory activity of the new conjugates on human 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) was investigated via in vitro radiosubstrate incubation. Some protected conjugates displayed moderate antiproliferative properties against a panel of human adherent cancer cell lines (the protected cytidine conjugate proved to be the most potent with IC50 value of 9 μM). The thymidine conjugate displayed considerable 17β-HSD1 inhibitory activity (IC50 = 19 μM). |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T04:57:24Z |
| publishDate | 2016-09-01 |
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| series | Molecules |
| spelling | doaj.art-4354bcb656b941719d262f1e82e0a0b42022-12-22T00:37:18ZengMDPI AGMolecules1420-30492016-09-01219121210.3390/molecules21091212molecules21091212Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside BioconjugatesBrigitta Bodnár0Erzsébet Mernyák1János Wölfling2Gyula Schneider3Bianka Edina Herman4Mihály Szécsi5Izabella Sinka6István Zupkó7Zoltán Kupihár8Lajos Kovács9Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, HungaryDepartment of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, HungaryDepartment of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, HungaryDepartment of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary1st Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720 Szeged, Hungary1st Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720 Szeged, HungaryDepartment of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, HungaryDepartment of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, HungaryDepartment of Medicinal Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, HungaryDepartment of Medicinal Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC). For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3′-hydroxy groups of the nucleosides were protected by acetyl groups and the 5′-hydroxy groups were modified by the tosyl–azide exchange method. The commonly used conditions for click reaction between the protected-5′-azidonucleosides and the steroid alkyne was slightly modified by using 1.5 equivalent of Cu(I) catalyst. All the prepared conjugates were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7 and A2780) and the potential inhibitory activity of the new conjugates on human 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) was investigated via in vitro radiosubstrate incubation. Some protected conjugates displayed moderate antiproliferative properties against a panel of human adherent cancer cell lines (the protected cytidine conjugate proved to be the most potent with IC50 value of 9 μM). The thymidine conjugate displayed considerable 17β-HSD1 inhibitory activity (IC50 = 19 μM).http://www.mdpi.com/1420-3049/21/9/1212nucleosides13α-estronecopper-catalyzed alkyne–azide click reactiontriazolesantiproliferative17β-HSD1 |
| spellingShingle | Brigitta Bodnár Erzsébet Mernyák János Wölfling Gyula Schneider Bianka Edina Herman Mihály Szécsi Izabella Sinka István Zupkó Zoltán Kupihár Lajos Kovács Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates Molecules nucleosides 13α-estrone copper-catalyzed alkyne–azide click reaction triazoles antiproliferative 17β-HSD1 |
| title | Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates |
| title_full | Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates |
| title_fullStr | Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates |
| title_full_unstemmed | Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates |
| title_short | Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates |
| title_sort | synthesis and biological evaluation of triazolyl 13α estrone nucleoside bioconjugates |
| topic | nucleosides 13α-estrone copper-catalyzed alkyne–azide click reaction triazoles antiproliferative 17β-HSD1 |
| url | http://www.mdpi.com/1420-3049/21/9/1212 |
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