Synthesis of novel 17-(5'-iodo)triazolyl-3-methoxyestrane epimers via Cu(I)-catalyzed azide-alkyne cycloadditon, and an evaluation of their cytotoxic activity in vitro

Steroids. 2015 Jun:98:153-65. doi: 10.1016/j.steroids.2015.02.018. Epub 2015 Feb 28.

Abstract

The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 3-methoxyestrane 17α- and 17β-azide epimers (3 and 5) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-f and 11a-f). If the Ph3P in the classical CuAAC process was replaced by Et3N, the formation of small quantities of 5-iodotriazoles (9a-f and 11a-f) was observed. For the preparation of 5-iodo-1,2,3-triazoles (9a-f and 11a-f), an improved method was developed, directly from steroidal azides and terminal alkynes, in reactions mediated by CuI and ICl as iodinating agents. The antiproliferative activities of the structurally related triazoles were determined in vitro with the microculture tetrazolium assay on six malignant human cell lines of gynecological origin (HeLa, A2780, MCF7, MDA-MB-231, MDA-MB-361 and T47D). X-ray analysis revealed the presence of the iodo substituent on the 1,2,3-triazole ring.

Keywords: 1,3-Dipolar cycloaddition; Cytotoxic activity; Iodotriazoles; X-ray analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Catalysis
  • Copper / chemistry*
  • Cytotoxins* / chemical synthesis
  • Cytotoxins* / chemistry
  • Cytotoxins* / pharmacology
  • Drug Screening Assays, Antitumor
  • Estranes* / chemical synthesis
  • Estranes* / chemistry
  • Estranes* / pharmacology
  • HeLa Cells
  • Humans
  • Hydrocarbons, Iodinated* / chemical synthesis
  • Hydrocarbons, Iodinated* / chemistry
  • Hydrocarbons, Iodinated* / pharmacology
  • MCF-7 Cells

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Estranes
  • Hydrocarbons, Iodinated
  • Copper