Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure

Liqiang Chen, Riccardo Petrelli, Guangyao Gao, Daniel J. Wilson, Garrett T. McLean, Hiremagalur N. Jayaram, Yuk Y. Sham, Krzysztof W. Pankiewicz

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Small molecules that act on multiple biological targets have been proposed to combat the drug resistance commonly observed for cancer chemotherapy. By combining the structural features of known inhibitors of inosine monophosphate dehydrogense (IMPDH) and histone deacetylase (HDAC), dual inhibitors of IMPDH and HDAC based on the scaffold of cinnamic hydroxamic acid (CHA) have been designed, synthesized, and evaluated in biological assays. Key features, including the linker length, linker functionality, substitution position, and interacting groups, have been explored. Their individual contribution to the inhibitory activities against human IMPDH1 and IMPDH2 as well as HDAC has been assessed.

Original languageEnglish (US)
Pages (from-to)5950-5964
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number16
DOIs
StatePublished - Aug 15 2010

Keywords

  • Cancer therapy
  • Cinnamic hydroxamic acid
  • Drug resistance
  • Dual inhibitor
  • Histone deacetylase
  • Inosine monophosphate dehydrogenase

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