Synthesis and in vitro pharmacological evaluation of N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]-carboxamides on d-secoestrone scaffolds

Johanna Szabó, Ildikó Bacsa, János Wölfling, Gyula Schneider, István Zupkó, Mónika Varga, Bianka E. Herman, László Kalmár, Mihály Szécsi, Erzsébet Mernyák

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12 Citations (Scopus)

Abstract

An efficient synthesis of several N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]carboxamides in the 13β- and 13α-d-secoestrone series is reported. Novel triazoles were synthesized via the Cu(I)-catalyzed azide-alkyne cycloaddition of steroidal alkynyl carboxamides and p-substituted benzyl azides. Each of the products was evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A431 and A2780). Some of them exhibited activities similar to those of the reference agent cisplatin. On change of the substitution pattern of the benzyl group of the azide, great differences in the cell growth-inhibitory properties were observed. The p-alkylbenzyl-substituted triazoles selectively exerted high cytostatic action against A2780 cells, with IC50 values of 1 μM. We investigated the potential inhibitory action exerted on the human 17β-HSD1 activity of the new secosteroids. Three triazoles effectively suppressed the estrone to 17β-estradiol conversion with IC50 values in low micromolar range.

Original languageEnglish
Pages (from-to)574-579
Number of pages6
JournalJournal of enzyme inhibition and medicinal chemistry
Volume31
Issue number4
DOIs
Publication statusPublished - Jul 3 2016

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Keywords

  • 17β-HSD1 inhibition
  • A2780
  • Antiproliferative effect
  • azide-alkyne cycloaddition
  • steroid

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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