New betulinic acid derivatives as potent proteasome inhibitors

Keduo Qian, Sang Yong Kim, Hsin Yi Hung, Li Huang, Chin Ho Chen, Kuo Hsiung Lee

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

In this study, 22 new betulinic acid (BA) derivatives were synthesized and tested for their inhibition of the chymotrypsin-like activity of 20S proteasome. From the SAR study, we concluded that the C-3 and C-30 positions are the pharmacophores for increasing the proteasome inhibition effects, and larger lipophilic or aromatic side chains are favored at these positions. Among the BA derivatives tested, compounds 13, 20, and 21 showed the best proteasome inhibition activity with IC 50 values of 1.42, 1.56, and 1.80 μM, respectively, which are three to fourfold more potent than the proteasome inhibition controls LLM-F and lactacystin.

Original languageEnglish
Pages (from-to)5944-5947
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number19
DOIs
Publication statusPublished - 2011 Oct 1

All Science Journal Classification (ASJC) codes

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

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