Chalcones as Novel Non-peptidic μ-Calpain Inhibitors

Abstract

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 (<TEX>$IC_{50}=16.67{\pm}0.42{\mu}M$</TEX>) and 8 (<TEX>$IC_{50}=16.92{\pm}0.14{\mu}M$</TEX>) in group A were most selective <TEX>${\mu}$</TEX>-calpain inhibitor over cathepsins B and L. On the other hand, compound 14 possessing furan ring exhibited inhibitory activities for <TEX>${\mu}$</TEX>-calpain (<TEX>$IC_{50}=15.39{\pm}1.34{\mu}M$</TEX>) as well as cathepsin B (<TEX>$IC_{50}=20.59{\pm}1.35{\mu}M$</TEX>). The results discovered implicated that chalcone analogues possessing proper size and functional groups can be a potential lead core for selective non-peptidic <TEX>${\mu}$</TEX>-calpain inhibitor. Furthermore, dual inhibitors for <TEX>${\mu}$</TEX>-calpain and cathepsin B can also be developed from chalcones by elaborate structure manipulation.