Synthesis and biological activity of pyrrole analogues of combretastatin A-4. Issue 13 (1st July 2016)

• Record Type: Journal Article
• Authors: Jung, Eun-Kyung; Leung, Euphemia; Barker, David
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 13(2016)
• Page Start: 3001
• Page End: 3005
• Publication Date: 2016-07-01
• Subjects: Pyrroles -- Combretastatin A-4 -- Antiproliferative agents -- Cancer -- Acyl-Claisen; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.026
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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-1 H -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-1 H -pyrrole35 exhibiting the most potent activity with IC50 value of 0.07 μM against MDA-MB-231 cell line.