Stereocontrolled synthesis of the four 16-hydroxymethyl-19-nortestosterone isomers and their antiproliferative activities

G. Schneider, Anita Kiss, E. Mernyák, Zsanett Benke, J. Wölfling, E. Frank, Noémi Bózsity, András Gyovai, Renáta Minorics, I. Zupkó

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Novel 16-hydroxymethyl-19-nortestosterone diastereomers were prepared by Birch reduction from the corresponding 3-methoxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol isomers with known configurations. The synthesized compounds are 16α- and 16β-hydroxymethyl-substituted 19-nortestosterone and their 17α-epimers. To prepare 17α-19-nortestosterone, the Mitsunobu inversion reaction of 19-nortestosterone with different alkyl and aryl carboxylic acids was chosen. Deacylation of the new compounds by the Zemplén method yielded the required 17α-19-nortestosterone. The antiproliferative activities of the structurally related compounds were determined in vitro through microculture tetrazolium assays on a panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF-7, MDA-MB-231, MDA-MB-361 and T47D) and ovarian (A2780) cell lines. The 17α epimer of 19-nortestosterone demonstrated considerable activity, selectively for HeLa cells, with a calculated IC50 of 0.65 μM. The reference compound, cisplatin, displayed an order of magnitude higher IC50 (12.4 μM). The cancer selectivity of 17α-19-nortestosterone was tested by MTT assay performed with noncancerous human fibroblast cell line MRC-5. The results indicated that 17α-19-nortestosterone selectively disturbs the viability of HeLa cells without greatly affecting other cancer cell types and intact fibroblasts.

Original languageEnglish
Pages (from-to)113-120
Number of pages8
JournalSteroids
Volume105
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • 17α-19-Nortestosterone
  • 19-Nortestosterone
  • Antiproliferative activity
  • Birch reduction
  • Stereocontrolled synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

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