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

作者：Chen Liqiang^*; Petrelli Riccardo; Gao Guangyao; Wilson Daniel J; McLean Garrett T; Jayaram Hiremagalur N; Sham Yuk Y; Pankiewicz Krzysztof W

来源：Bioorganic & Medicinal Chemistry, 2010, 18(16): 5950-5964.

DOI：10.1016/j.bmc.2010.06.081

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

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.

• 出版日期2010-8-15