A boronic acid chalcone analog of combretastatin A-4 as a potent anti-proliferation agent

Yali Kong, Kan Wang, Michael C. Edler, Ernest Hamel, Susan L. Mooberry, Mikell A. Paige, Milton L. Brown

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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 GI50-values below 10 nM. Furthermore, this drug has significant anti-angiogenesis effects demonstrated by HUVEC tube formation and aortic ring assay.

Original languageEnglish (US)
Pages (from-to)971-977
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number2
DOIs
StatePublished - Jan 15 2010

Keywords

  • Anti-tumor agent
  • Boronic acid
  • Chalcone
  • Combretastatin A-4
  • Tubulin polymerization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'A boronic acid chalcone analog of combretastatin A-4 as a potent anti-proliferation agent'. Together they form a unique fingerprint.

Cite this