Antivascular and anticancer activity of dihalogenated A-ring analogues of combretastatin A-4Electronic supplementary information (ESI) available: Experimental procedures for the synthesis of 5 and 23-26 with full spectral data, along with procedures for HUVEC isolation, biological assays and microscopy methods. See DOI: 10.1039/c0md00095g

• Main Authors: Beale, Thomas M, Myers, Rebecca M, Shearman, James W, Charnock-Jones, D. Stephen, Brenton, James D, Gergely, Fanni V, Ley, Steven V
• Format: Journal Article
• Language: English
• Published: 01.09.2010
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c0md00095g

The generally accepted view is that the 3,4,5-trimethoxy-substituted aromatic A-ring of combretastatin A-4 (CA-4) and its analogues should be conserved in order to maintain biological activity through enforcing an active molecular conformation. Contrary to this, we have found that substituting the larger meta -methoxy groups of CA-4 with smaller halogen atoms results in compounds that are equipotent or more potent than CA-4 itself in vitro . The anticancer and antivascular activity of dihalogenated A-ring analogues of CA-4 depends strongly on the nature of the halogen. Dibrominated and diiodinated analogues displayed low nM activity against endothelial cells and a greater percentage of mitotic arrest in ovarian carcinoma cells when compared to CA-4.