Stereoselective synthesis of new type of estradiol hybrid molecules and their antiproliferative activities

Anita Kiss, J. Wölfling, E. Mernyák, E. Frank, András Gyovai, Ágnes Kulmány, I. Zupkó, G. Schneider

Research output: Contribution to journalArticle

Abstract

To prepare new type of estrane hybrid molecules, we chose 3-methoxy- and 3-benzyloxy-17β,16β-epoxymethylene-estra-1,3,5(10)-trienes as starting materials (2 and 5). These steroid oxetanes were transformed with ethylene glycol in the presence of BF 3 .OEt 2 into 3-methoxy- and 3-benzyloxy-16β-(2′-oxa-4′-hydroxy)butyl-17β-hydroxy-estra-1,3,5(10)-trien-17β-ols (3a and 6a). Iodination of the terminal hydroxy group afforded iodo derivatives 3b and 6b, which underwent one-pot 3-O-alkylation with unprotected ascorbic acid to yield 3c and 6c. The same process with salicylic acid led to 2-O-alkylated salicylic acid derivatives 3d and 6d. Iodo derivatives 3b and 6b underwent nucleophilic exchange reaction with NaN 3 furnishing the corresponding azido compounds 3e and 6e. These compounds were subjected to azide–alkyne CuAAC reactions with phenylacetylene and their p-substituted derivatives to form 1,4-substituted triazoles 3f-h and 6f-h. The reduction of 3e and 6e with hydrazine hydrate in the presence of Raney Ni provided the corresponding amino derivatives 3i and 6i. These compounds were reacted further with varied substituted benzoic acids to deliver terminal benzamido derivatives 3j-m and 6j-m. We determined the in vitro antiproliferative activities of compounds 2, 5, 3a-m and 6a-m by means of MTT assays on a panel of human adherent cancer cell lines A2780, MCF-7, MB-231 and SiHa.

Original languageEnglish
Pages (from-to)63-72
Number of pages10
JournalSteroids
Volume148
DOIs
Publication statusPublished - Aug 1 2019

Fingerprint

hydrazine
Salicylic Acid
Estranes
Estradiol
Trientine
Derivatives
Molecules
Triazoles
Ethylene Glycol
Halogenation
Benzoates
Alkylation
Ascorbic Acid
Steroids
Cell Line
Neoplasms
Assays
Cells
phenylacetylene
In Vitro Techniques

Keywords

  • 3-Methoxy-, 3-Benzyloxy-estra-1,3,5(10)-trienes
  • Hybrid molecules
  • Linker
  • Oxetanes

ASJC Scopus subject areas

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

Cite this

Stereoselective synthesis of new type of estradiol hybrid molecules and their antiproliferative activities. / Kiss, Anita; Wölfling, J.; Mernyák, E.; Frank, E.; Gyovai, András; Kulmány, Ágnes; Zupkó, I.; Schneider, G.

In: Steroids, Vol. 148, 01.08.2019, p. 63-72.

Research output: Contribution to journalArticle

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AU - Frank, E.

AU - Gyovai, András

AU - Kulmány, Ágnes

AU - Zupkó, I.

AU - Schneider, G.

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