Chalcones as novel non-peptidic μ-calpain inhibitors

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 (IC₅₀ = 16.67 ± 0.42 μM) and 8 (IC₅₀ = 16.92 ± 0.14 μM) in group A were most selective μ-calpain inhibitor over cathepsins B and L. On the other hand, compound 14 possessing furan ring exhibited inhibitory activities for μ-calpain (IC₅₀ = 15.39 ± 1.34 μM) as well as cathepsin B (IC₅₀ = 20.59 ± 1.35 μM). The results discovered implicated that chalcone analogues possessing proper size and functional groups can be a potential lead core for selective non-peptidic μ-calpain inhibitor. Furthermore, dual inhibitors for μ-calpain and cathepsin B can also be developed from chalcones by elaborate structure manipulation.