Chalcones as Novel Non-peptidic μ-Calpain Inhibitors

• Published in: Bulletin of the Korean Chemical Society Vol. 32; no. 9; pp. 3459 - 3464
• Main Authors: Lee, Eun-Young, Jang, In-Hye, Shin, Min-Jung, Cho, Hee-Ju, Kim, Jung-Sook, Eom, Ji-Eun, Kwon, Young-Joo, Na, Young-Hwa
• Format: Journal Article
• Language: Korean
• Published: 2011
• Subjects: Cathepsin B & L; Calpain inhibitor; Chalcone
• ISSN: 0253-2964; 1229-5949

In order to extend the scaffold of non-peptidic calpain inhibitor, we have designed and synthesized 14 chalcone derivatives categorized into two groups based on their structures. Compounds 7 ($IC_{50}=16.67{\pm}0.42{\mu}M$) and 8 ($IC_{50}=16.92{\pm}0.14{\mu}M$) in group A were most selective ${\mu}$-calpain inhibitor over cathepsins B and L. On the other hand, compound 14 possessing furan ring exhibited inhibitory activities for ${\mu}$-calpain ($IC_{50}=15.39{\pm}1.34{\mu}M$) as well as cathepsin B ($IC_{50}=20.59{\pm}1.35{\mu}M$). The results discovered implicated that chalcone analogues possessing proper size and functional groups can be a potential lead core for selective non-peptidic ${\mu}$-calpain inhibitor. Furthermore, dual inhibitors for ${\mu}$-calpain and cathepsin B can also be developed from chalcones by elaborate structure manipulation.