title: Synthesis and biological evaluations of new analogs of 2-methoxyestradiol: inhibitors of tubulin and angiogenesis.
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.
authors.affiliation: 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.
authors.forename: Eirik Johansson
authors.initials: EJ
authors.lastname: Solum
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan; Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan. Electronic address: verona@nricm.edu.tw.
authors.forename: Jing-Jy
authors.initials: JJ
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway. Electronic address: i.b.sorvik@farmasi.uio.no.
authors.forename: Irene B
authors.initials: IB
authors.lastname: Sørvik
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway. Electronic address: r.e.paulsen@farmasi.uio.no.
authors.forename: Ragnhild E
authors.initials: RE
authors.lastname: Paulsen
authors.affiliation: 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.
authors.forename: Anders
authors.initials: A
authors.lastname: Vik
authors.affiliation: 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.
authors.forename: Trond Vidar
authors.initials: TV
authors.lastname: Hansen
mesh_terms: D000077584:2-Methoxyestradiol; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D050257:Tubulin Modulators; D004958:Estradiol; D000077584:2-Methoxyestradiol
keywords: 2-Methoxyestradiol; Anti-angiogenesis; Anti-cancer; Steroids; Tubulin inhibition