Synthesis and biological evaluation of triazolyl 13α-estrone-nucleoside bioconjugates

Brigitta Bodnár, E. Mernyák, J. Wölfling, G. Schneider, Bianka Edina Herman, Mihály Szécsi, Izabella Sinka, I. Zupkó, Zoltán Kupihár, L. Kovács

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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).

Original languageEnglish
Article number1212
JournalMolecules
Volume21
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

nucleosides
Alkynes
Azides
Estrone
Nucleosides
Cells
Cytidine
Inhibitory Concentration 50
evaluation
synthesis
Thymidine
Functional groups
Copper
Cell Line
Assays
dehydrogenases
Steroids
alkynes
cultured cells
Catalysts

Keywords

  • 13α-estrone
  • 17β-hsd1
  • Antiproliferative
  • Copper-catalyzed alkyne-azide click reaction
  • Nucleosides
  • Triazoles

ASJC Scopus subject areas

  • Medicine(all)
  • Organic Chemistry

Cite this

Synthesis and biological evaluation of triazolyl 13α-estrone-nucleoside bioconjugates. / Bodnár, Brigitta; Mernyák, E.; Wölfling, J.; Schneider, G.; Herman, Bianka Edina; Szécsi, Mihály; Sinka, Izabella; Zupkó, I.; Kupihár, Zoltán; Kovács, L.

In: Molecules, Vol. 21, No. 9, 1212, 01.09.2016.

Research output: Contribution to journalArticle

Bodnár, Brigitta ; Mernyák, E. ; Wölfling, J. ; Schneider, G. ; Herman, Bianka Edina ; Szécsi, Mihály ; Sinka, Izabella ; Zupkó, I. ; Kupihár, Zoltán ; Kovács, L. / Synthesis and biological evaluation of triazolyl 13α-estrone-nucleoside bioconjugates. In: Molecules. 2016 ; Vol. 21, No. 9.
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AU - Herman, Bianka Edina

AU - Szécsi, Mihály

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AB - 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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