Show simple item record

dc.contributor.authorSolum, Eirik Johansson
dc.contributor.authorCheng, Jing-Jy
dc.contributor.authorSylte, Ingebrigt
dc.contributor.authorVik, Anders
dc.contributor.authorHansen, Trond Vidar
dc.date.accessioned2016-03-31T15:09:05Z
dc.date.available2016-03-31T15:09:05Z
dc.date.issued2015-03-27
dc.description.abstractThe synthesis, cytotoxicity, inhibition of tubulin polymerization and anti-angiogenic effects of 10 analogs of 2-methoxyestradiol are reported. These efforts revealed that the analog with a 4-pyridine ring in the 17-position, in combination with 2-ethyl- and 3-sulfamate substituents on the steroid A-ring, is the most interesting anti-cancer agent. This compound showed potent inhibitory effects against angiogenesis (IC50 = 0.1 ± 0.02 μM) and selective cytotoxic effects towards the CEM, H460 and HT-29 cancer cell lines, with no cytotoxicity observed against the healthy VERO cell line. The most interesting analog also displayed inhibition of tubulin polymerization (IC50 = 4.3 μM) almost as potent as 2-methoxyestradiol (IC50 = 3.5 μM). Molecular modeling experiments showed that this analog interacts within the colchicine-binding site of β-tubulin via multiple bonding with several amino acids. These observations provide support that the cytotoxic and anti-angiogenic effects observed for this novel analog are, at least in part, mediated by binding to tubulin.en_US
dc.descriptionPublished version. Source at <a href=http://doi.org/10.1039/c5ra03570h>http://doi.org/10.1039/c5ra03570h</a>.en_US
dc.identifier.citationRSC Advances 2015, 5(41):32497-32504en_US
dc.identifier.cristinIDFRIDAID 1241412
dc.identifier.doi10.1039/c5ra03570h
dc.identifier.issn2046-2069
dc.identifier.urihttps://hdl.handle.net/10037/9085
dc.identifier.urnURN:NBN:no-uit_munin_8648
dc.language.isoengen_US
dc.publisherRoyal Society of Chemistryen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Kjemi: 440en_US
dc.titleSynthesis, biological evaluation and molecular modeling of new analogs of the anti-cancer agent 2-methoxyestradiol: potent inhibitors of angiogenesisen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record