Synthesis and biological evaluations of new analogs of 2-methoxyestradiol: inhibitors of tubulin and angiogenesis

Eirik Johansson Solum; Jing-Jy Cheng; Irene B Sørvik; Ragnhild E Paulsen; Anders Vik; Trond Vidar Hansen

doi:10.1016/j.ejmech.2014.08.002

Synthesis and biological evaluations of new analogs of 2-methoxyestradiol: inhibitors of tubulin and angiogenesis

Eur J Med Chem. 2014 Oct 6:85:391-8. doi: 10.1016/j.ejmech.2014.08.002. Epub 2014 Aug 2.

Authors

Eirik Johansson Solum¹, Jing-Jy Cheng², Irene B Sørvik³, Ragnhild E Paulsen⁴, Anders Vik⁵, Trond Vidar Hansen⁶

Affiliations

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, PO Box 1068, Blindern, N-0316 Oslo, Norway. Electronic address: e.j.solum@farmasi.uio.no.
² National Research Institute of Chinese Medicine, Taipei, Taiwan; Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan. Electronic address: verona@nricm.edu.tw.
³ Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway. Electronic address: i.b.sorvik@farmasi.uio.no.
⁴ Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway. Electronic address: r.e.paulsen@farmasi.uio.no.
⁵ Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, PO Box 1068, Blindern, N-0316 Oslo, Norway. Electronic address: anders.vik@farmasi.uio.no.
⁶ Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, PO Box 1068, Blindern, N-0316 Oslo, Norway. Electronic address: t.v.hansen@farmasi.uio.no.

PMID: 25108078
DOI: 10.1016/j.ejmech.2014.08.002

Abstract

The synthesis, cytotoxicity, inhibition of tubulin polymerization and anti-angiogenic effects of 15 analogs of 2-methoxyestradiol (1) are reported. The biological studies revealed that the position of nitrogen atom in the heterocyclic ring is important for inhibition of both tubulin polymerization and angiogenesis. The most potent inhibitors were compounds 11f and 13e, with a 6-substituted isoquinoline ring in the 17-position of the steroid skeleton. Moreover, low estrogen activity was observed for the analogs tested at 10 μM concentrations.

Keywords: 2-Methoxyestradiol; Anti-angiogenesis; Anti-cancer; Steroids; Tubulin inhibition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

2-Methoxyestradiol
Angiogenesis Inhibitors / chemical synthesis*
Angiogenesis Inhibitors / chemistry
Angiogenesis Inhibitors / pharmacology*
Cell Line, Tumor
Chemistry Techniques, Synthetic
Drug Design*
Estradiol / analogs & derivatives*
Estradiol / chemical synthesis
Estradiol / chemistry
Estradiol / pharmacology
Humans
Inhibitory Concentration 50
Structure-Activity Relationship
Tubulin Modulators / chemical synthesis*
Tubulin Modulators / chemistry
Tubulin Modulators / pharmacology*

Substances

Angiogenesis Inhibitors
Tubulin Modulators
Estradiol
2-Methoxyestradiol