dc.contributor.author | GREENE, LISA | |
dc.contributor.author | ZISTERER, DANIELA MARIA | |
dc.contributor.author | MEEGAN, MARY JANE | |
dc.contributor.author | LLOYD, DAVID G | |
dc.date.accessioned | 2010-12-10T12:18:36Z | |
dc.date.available | 2010-12-10T12:18:36Z | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010 | en |
dc.identifier.citation | Miriam Carr, Lisa M. Greene, Andrew J.S. Knox, David G Lloyd, Daniela M. Zisterer and Mary J. Meegan, Lead identification of conformationally restricted ?-lactam type combretastatin analogues: synthesis, antiproliferative activity and tubulin targeting effects, European Journal of Medicinal Chemistry, 45, 12, 2010, 5752-5766 | en |
dc.identifier.other | Y | |
dc.description | PUBLISHED | en |
dc.description.abstract | The synthesis and study of the structure-activity relationships of a series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (?-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. The 1,4-diaryl-2-azetidinones are unsubstituted at C-3, or contain methyl substituent(s) at C-3. The most potent compounds 12d and 12e display antiproliferative activity at nanomolar concentrations when evaluated against the MCF-7 and MDA-MB-231 human breast carcinoma cell lines. 12d exerts antimitotic effects through an inhibition of tubulin polymerisation and subsequent G2/M arrest of the cell cycle in human MDA-MB-231 breast cancer cells, with similar activity to that of CA-4. These novel ?-lactam compounds are identified as potentially useful scaffolds for the further development of antitumour agents which target tubulin. | en |
dc.description.sponsorship | This work was supported through funding from the Trinity College IITAC research initiative (HEA PRTLI), Enterprise Ireland (EI), Science Foundation Ireland (SFI), and the Health Research Board (HRB), with additional support for computational facilities from the Wellcome Trust. A postgraduate research award from Trinity College is gratefully acknowledged. | en |
dc.format.extent | 5752-5766 | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.relation.ispartofseries | European Journal of Medicinal Chemistry; | |
dc.relation.ispartofseries | 45; | |
dc.relation.ispartofseries | 12; | |
dc.rights | Y | en |
dc.subject | Biochemistry | en |
dc.subject | beta-lactam | en |
dc.title | Lead identification of conformationally restricted ?-lactam type combretastatin analogues: synthesis, antiproliferative activity and tubulin targeting effects | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/lloyddg | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/greeneli | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/dzistrer | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/mmeegan | |
dc.identifier.rssinternalid | 68624 | |
dc.identifier.rssuri | http://dx.doi.org/10.1016/j.ejmech.2010.09.033 | en |
dc.contributor.sponsor | Higher Education Authority | en |
dc.contributor.sponsor | Science Foundation Ireland | |
dc.contributor.sponsor | Health Research Board | |
dc.contributor.sponsor | Enterprise Ireland | |
dc.identifier.uri | http://hdl.handle.net/2262/41266 | |