Synthesis of trans-16-triazolyl-13α-methyl-17-estradiol diastereomers and the effects of structural modifications on their in vitro antiproliferative activities

E. Mernyák, Ida Kovács, Renáta Minorics, Péter Sere, Dóra Czégány, Izabella Sinka, J. Wölfling, G. Schneider, Zsuzsanna Újfaludi, I. Boros, I. Ocsovszki, Mónika Varga, I. Zupkó

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Novel 16-triazoles in the 13α-estrone series were synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition of the two diastereomeric (on C-16 and on C-17) 16-azido-13α-estra-1,3,5(10)-trien-17-ol 3-benzyl ethers with substituted phenylacetylenes. The new heterocyclic derivatives were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A431, A2780, T47D, MDA-MB-231 and MDA-MB-361). The inversion of the configurations at C-16 and C-17 selectively affected the growth-inhibitory properties of the tested compounds. The 16β,17α isomers generally proved to be potent on all cell lines, with IC50 values comparable to those of the reference agent cisplatin. Change of the substitution pattern of the phenyl group of the acetylene led to great differences in antiproliferative properties. Exclusively the p-phenyl-substituted triazoles exerted high cytostatic effects. One of the most potent compounds activated caspase-3 and caspase-9 without influencing caspase-8, confirming the induction of apoptosis via the intrinsic pathway.

Original languageEnglish
Pages (from-to)123-134
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume150
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Triazoles
Estradiol
Cells
Trientine
Cell Line
Acetylene
Alkynes
Ethers
Azides
Cycloaddition
Caspase 9
Caspase 8
Estrone
Cycloaddition Reaction
Cytostatic Agents
Caspase 3
Isomers
Cisplatin
Inhibitory Concentration 50
Assays

Keywords

  • 13α-estradiol
  • Antiproliferative effect
  • Apoptosis
  • Azide-alkyne cycloaddition
  • Cell cycle blockade

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Molecular Medicine
  • Medicine(all)

Cite this

Synthesis of trans-16-triazolyl-13α-methyl-17-estradiol diastereomers and the effects of structural modifications on their in vitro antiproliferative activities. / Mernyák, E.; Kovács, Ida; Minorics, Renáta; Sere, Péter; Czégány, Dóra; Sinka, Izabella; Wölfling, J.; Schneider, G.; Újfaludi, Zsuzsanna; Boros, I.; Ocsovszki, I.; Varga, Mónika; Zupkó, I.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 150, 01.06.2015, p. 123-134.

Research output: Contribution to journalArticle

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AU - Mernyák, E.

AU - Kovács, Ida

AU - Minorics, Renáta

AU - Sere, Péter

AU - Czégány, Dóra

AU - Sinka, Izabella

AU - Wölfling, J.

AU - Schneider, G.

AU - Újfaludi, Zsuzsanna

AU - Boros, I.

AU - Ocsovszki, I.

AU - Varga, Mónika

AU - Zupkó, I.

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