||Design, Synthesis and Biological Evaluation of a Structurally Simplified Syringolin A Analogues
Chiba, Takuya ,
Kitahata, Shun Matsuda, Akira ,
Chemical & pharmaceutical bulletin
816 , 2016-07 , The Pharmaceutical Society of Japan （日本薬学会）
In this study, we designed and synthesized a structurally simplified syringolin A analogue 4, which could have a switched hydrogen bonding interaction with the beta 5 subunit of 20S proteasome. This analogue exhibits potent beta 5 proteasome inhibitory activity with an IC50 value of 107 nM. It also shows cytotoxicity against a range of human cancer cells at submicromolar level (109-254 nM). This analogue is expected to be a lead compound as a next generation proteasome inhibitor because of its simple structure.