Discovery of 4-aryl-2-benzoyl-imidazoles as tubulin polymerization inhibitor with potent antiproliferative properties

Min Xiao, Sunjoo Ahn, Jin Wang, Jianjun Chen, Duane Miller, James T. Dalton, Wei Li

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

A series of 4-aryl-2-benzoyl-imidazoles were designed and synthesized based on our previously reported 2-aryl-4-benzoyl-imidazole (ABI) derivatives. The new structures reversed the aryl group and the benzoyl group of previous ABI structures and were named as reverse ABI (RABI) analogues. RABIs were evaluated for biological activity against eight cancer cell lines including multidrug-resistant cancer cell lines. In vitro assays indicated that several RABI compounds had excellent antiproliferative properties, with IC50 values in the low nanomolar range. The average IC50 of the most active compound 12a is 14 nM. In addition, the mechanism of action of these new analogues was investigated by cell cycle analysis, tubulin polymerization assay, competitive mass spectrometry binding assay, and molecular docking studies. These studies confirmed that these new RABI analogues maintain their mechanisms of action by disrupting tubulin polymerization, similar to their parental ABI analogues.

Original languageEnglish (US)
Pages (from-to)3318-3329
Number of pages12
JournalJournal of Medicinal Chemistry
Volume56
Issue number8
DOIs
StatePublished - Apr 25 2013

Fingerprint

Tubulin Modulators
Imidazoles
Tubulin
Polymerization
Inhibitory Concentration 50
Cell Line
Mass Spectrometry
Neoplasms
Cell Cycle
imidazole

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Discovery of 4-aryl-2-benzoyl-imidazoles as tubulin polymerization inhibitor with potent antiproliferative properties. / Xiao, Min; Ahn, Sunjoo; Wang, Jin; Chen, Jianjun; Miller, Duane; Dalton, James T.; Li, Wei.

In: Journal of Medicinal Chemistry, Vol. 56, No. 8, 25.04.2013, p. 3318-3329.

Research output: Contribution to journalArticle

Xiao, Min ; Ahn, Sunjoo ; Wang, Jin ; Chen, Jianjun ; Miller, Duane ; Dalton, James T. ; Li, Wei. / Discovery of 4-aryl-2-benzoyl-imidazoles as tubulin polymerization inhibitor with potent antiproliferative properties. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 8. pp. 3318-3329.
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