A facile 'click' approach to novel 15β-triazolyl-5α-androstane derivatives, and an evaluation of their antiproliferative activities in vitro

Zalán Kádár, Judit Molnár, G. Schneider, I. Zupkó, E. Frank

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Intermolecular Cu(I)-catalyzed azide-alkyne cycloadditions of 15β-azido-17β-hydroxy-5α-androstan-3β-yl acetate with different terminal alkynes under optimized reaction conditions were carried out to furnish 15β-triazolyl derivatives in good yields. Subsequent oxidation of the 'click' products with the Jones reagent afforded the corresponding 17-ketones. All the synthetized compounds were tested on three malignant human cell lines (HeLa, MCF7 and A431) in order to investigate their antiproliferative activities in vitro. Evidence of cell cycle blockade and apoptosis induction was obtained for the most effective five selected compounds by means of flow cytometry and microscopic techniques. The 15β-triazolyl-5α-androstane framework may be considered an appropriate base for the design of steroidal antiproliferative agents.

Original languageEnglish
Pages (from-to)1396-1402
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number4
DOIs
Publication statusPublished - Feb 15 2012

Fingerprint

Alkynes
Cells
Derivatives
Azides
Cycloaddition
Flow cytometry
Cycloaddition Reaction
Ketones
Cell Cycle
Flow Cytometry
Acetates
Apoptosis
Cell Line
Oxidation
androstane
In Vitro Techniques

Keywords

  • 1,3-Dipolar cycloaddition
  • Antiproliferative activity
  • Cu(I) catalysis
  • Steroidal azides
  • Triazoles

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

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abstract = "Intermolecular Cu(I)-catalyzed azide-alkyne cycloadditions of 15β-azido-17β-hydroxy-5α-androstan-3β-yl acetate with different terminal alkynes under optimized reaction conditions were carried out to furnish 15β-triazolyl derivatives in good yields. Subsequent oxidation of the 'click' products with the Jones reagent afforded the corresponding 17-ketones. All the synthetized compounds were tested on three malignant human cell lines (HeLa, MCF7 and A431) in order to investigate their antiproliferative activities in vitro. Evidence of cell cycle blockade and apoptosis induction was obtained for the most effective five selected compounds by means of flow cytometry and microscopic techniques. The 15β-triazolyl-5α-androstane framework may be considered an appropriate base for the design of steroidal antiproliferative agents.",
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author = "Zal{\'a}n K{\'a}d{\'a}r and Judit Moln{\'a}r and G. Schneider and I. Zupk{\'o} and E. Frank",
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AU - Kádár, Zalán

AU - Molnár, Judit

AU - Schneider, G.

AU - Zupkó, I.

AU - Frank, E.

PY - 2012/2/15

Y1 - 2012/2/15

N2 - Intermolecular Cu(I)-catalyzed azide-alkyne cycloadditions of 15β-azido-17β-hydroxy-5α-androstan-3β-yl acetate with different terminal alkynes under optimized reaction conditions were carried out to furnish 15β-triazolyl derivatives in good yields. Subsequent oxidation of the 'click' products with the Jones reagent afforded the corresponding 17-ketones. All the synthetized compounds were tested on three malignant human cell lines (HeLa, MCF7 and A431) in order to investigate their antiproliferative activities in vitro. Evidence of cell cycle blockade and apoptosis induction was obtained for the most effective five selected compounds by means of flow cytometry and microscopic techniques. The 15β-triazolyl-5α-androstane framework may be considered an appropriate base for the design of steroidal antiproliferative agents.

AB - Intermolecular Cu(I)-catalyzed azide-alkyne cycloadditions of 15β-azido-17β-hydroxy-5α-androstan-3β-yl acetate with different terminal alkynes under optimized reaction conditions were carried out to furnish 15β-triazolyl derivatives in good yields. Subsequent oxidation of the 'click' products with the Jones reagent afforded the corresponding 17-ketones. All the synthetized compounds were tested on three malignant human cell lines (HeLa, MCF7 and A431) in order to investigate their antiproliferative activities in vitro. Evidence of cell cycle blockade and apoptosis induction was obtained for the most effective five selected compounds by means of flow cytometry and microscopic techniques. The 15β-triazolyl-5α-androstane framework may be considered an appropriate base for the design of steroidal antiproliferative agents.

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