Synthesis, cytotoxic effects and tubulin polymerization inhibition of 1,4-disubstituted 1,2,3-triazole analogs of 2-methoxyestradiol

• Analogs of the steroid metabolite 2-methoxyestradiol were prepared as potential new anti-cancer agents.
• Cytotoxic effects in the low micromolar range were observed for some analogs.
• The most cytotoxic and interesting analogs also exhibited tubulin inhibition.
• The 1,4-disubstitued-1,2,3-analogs were obtained with excellent diastero- and regioselectivity.

Thirteen 1,4-disubstituted 1,2,3-triazole analogs of 2-methoxyestradiol were prepared and tested for their cytotoxic and tubulin polymerization inhibition effects. Two compounds, 11j and 11k, exhibited anti-proliferative effects at low micromolar concentrations. The two analogs 11j and 11k also inhibited tubulin assembly with IC50 values of 8.1 and 5.9 μM, respectively.

Figure optionsDownload as PowerPoint slide