New betulinic acid derivatives as potent proteasome inhibitors

作者：Qian Keduo^*; Kim Sang Yong; Hung Hsin Yi; Huang Li; Chen Chin Ho; Lee Kuo Hsiung

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(19): 5944-5947.

DOI：10.1016/j.bmcl.2011.07.072

• Betulinic acid derivatives
• Proteasome inhibitors

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 mu M, respectively, which are three to fourfold more potent than the proteasome inhibition controls LLM-F and lactacystin.

• 出版日期2011-10-1
• 单位中国医科大学