1. Academic Validation
  2. Synthesis and biological evaluations of new analogs of 2-methoxyestradiol: inhibitors of tubulin and angiogenesis

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.
Eirik Johansson Solum 1 Jing-Jy Cheng 2 Irene B Sørvik 3 Ragnhild E Paulsen 4 Anders Vik 5 Trond Vidar Hansen 6
Affiliations

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.
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.

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