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

Eirik Johansson Solum; Anders Vik; Trond Vidar Hansen

doi:10.1016/j.steroids.2014.05.020

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

Steroids. 2014 Sep:87:46-53. doi: 10.1016/j.steroids.2014.05.020. Epub 2014 Jun 9.

Authors

Eirik Johansson Solum¹, Anders Vik¹, Trond Vidar Hansen²

Affiliations

¹ School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068, Blindern, N-0316 Oslo, Norway.
² School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068, Blindern, N-0316 Oslo, Norway. Electronic address: t.v.hansen@farmasi.uio.no.

PMID: 24923521
DOI: 10.1016/j.steroids.2014.05.020

Abstract

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 5.9μM, respectively.

Keywords: 1,2,3-Triazoles; 2-Methoxyestradiol; Anti-cancer; Cytotoxicity; Estrogens; Tubulin inhibition.

MeSH terms

2-Methoxyestradiol
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Chemistry Techniques, Synthetic
Estradiol / analogs & derivatives*
Estradiol / chemical synthesis
Estradiol / chemistry
Estradiol / pharmacology
Humans
K562 Cells
Protein Multimerization / drug effects*
Protein Structure, Quaternary
Triazoles / chemistry*
Tubulin / chemistry*
Tubulin Modulators / chemical synthesis
Tubulin Modulators / chemistry
Tubulin Modulators / pharmacology

Substances

Antineoplastic Agents
Triazoles
Tubulin
Tubulin Modulators
Estradiol
2-Methoxyestradiol