title: Synthesis and biological activity of pyrrole analogues of combretastatin A-4.
abstract: A series of pyrrole analogues of combretastatin (CA-4) were synthesized and tested for their anti-proliferative activity. The highly diastereoselective acyl-Claisen rearrangement was used to provide 2,3-syn disubstituted morpholine amides which were used as precursors for the various analogues. This synthesis allows for the preparation of 1,2- and 2,3-diaryl-1H-pyrroles which are both geometrically similar to CA-4. These pyrrolic analogues were tested for their anti-proliferative activity against two human cell lines, K562 and MDA-MB-231 with 2,3-diaryl-1H-pyrrole 35 exhibiting the most potent activity with IC50 value of 0.07μM against MDA-MB-231 cell line.
authors.affiliation: School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland, New Zealand.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Jung
authors.affiliation: Auckland Cancer Society Research Centre and Department of Molecular Medicine and Pathology, University of Auckland, New Zealand.
authors.forename: Euphemia
authors.initials: E
authors.lastname: Leung
authors.affiliation: School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland, New Zealand. Electronic address: d.barker@auckland.ac.nz.
authors.forename: David
authors.initials: D
authors.lastname: Barker
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000621099:2'-methoxy-5'-(1-(4'-methoxybenzyl)-4,5-dimethyl-3-(3'',4'',5''-trimethoxyphenyl)-1H-pyrrol-2-yl)phenol; D000970:Antineoplastic Agents; D011758:Pyrroles; D013267:Stilbenes; D006139:Guaiacol; C058728:fosbretabulin
keywords: Acyl-Claisen; Antiproliferative agents; Cancer; Combretastatin A-4; Pyrroles