Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 18, Issue 2, Pages 971-977Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2009.11.003
Keywords
Chalcone; Boronic acid; Combretastatin A-4; Tubulin polymerization; Anti-tumor agent
Funding
- National Cancer Institute's Developmental Therapeutics Program
- Georgetown Medical Center Drug Discovery Program
- Lombardi Comprehensive Cancer Center
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Chalcones represent a class of natural products that inhibits tubulin assembly. In this study we designed and synthesized boronic acid analogs of chalcones in an effort to compare biological activities with combretastatin A-4, a potent inhibitor of tubulin polymerization. Systematic evaluation of the positional effects of the carbonyl moiety towards inhibition of tubulin polymerization, cancer cell proliferation and angiogenesis revealed that placement of the carbonyl adjacent to the trimethoxybenzene A-ring resulted in more active compounds than when the carbonyl group was placed adjacent to the C-ring. Our study identified a boronic acid chalcone with inhibition towards 16 human cancer cell lines in the 10-200 nM range, and another three cell lines with GI(50)-values below 10 nM. Furthermore, this drug has significant anti-angiogenesis effects demonstrated by HUVEC tube formation and aortic ring assay. (C) 2009 Elsevier Ltd. All rights reserved.
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