Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anticancer agents

Rong He, Yufeng Chen, Yihua Chen, Andrei V. Ougolkov, Jin San Zhang, Doris N. Savoy, Daniel D. Billadeau, Alan P. Kozikowski

Research output: Contribution to journalArticle

54 Scopus citations


Our triazole-based histone deacetylase inhibitor (HDACI), octanedioic acid hydroxyamide[3-(1-phenyl-1H-[1,2,3]triazol-4-yl)phenyl]amide (4a), suppresses pancreatic cancer cell growth in vitro with the lowest IC50 value of 20nM against MiaPaca-2 cell. In this study, we continued our efforts to develop triazol-4-ylphenyl bearing hydroxamate analogues by embellishing the terminal phenyl ring of 4a with different substituents. The isoform inhibitory profile of these hydroxamate analogues was similar to those of 4a. All of these triazol-4-ylphenyl bearing hydroxamates are pan-HDACIs like SAHA. Moreover, compounds 4h and 11a were found to be very effective inhibitors of cancer cell growth in the HupT3 (IC50=50 nM) and MiaPaca-2 (IC50=40 nM) cancer cell lines, respectively. Compound 4a was found to reactivate the expression of CDK inhibitor proteins and to suppress pancreatic cancer cell growth in vivo. Taken together, these data further support the value of the triazol-4-ylphenyl bearing hydroxamates in identifying potential pancreatic cancer therapies.

Original languageEnglish (US)
Pages (from-to)1347-1356
Number of pages10
JournalJournal of Medicinal Chemistry
Issue number3
StatePublished - Mar 1 2010


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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