College of Pharmacy, Graduate School of Pharmaceutical Sciences, Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
Bioorg Chem. 2013 Dec;51:24-30. doi: 10.1016/j.bioorg.2013.09.002. Epub 2013 Sep 16.
In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active inhibitory activity against m-calpain with an IC50 value of 25.25±0.901μM. With respect to inhibition of cathepsins B and L, compound 13 exhibited the most potent inhibitory activity on cathepsin L and moderate inhibitory activity on cathepsin B with IC50 values of 2.80±0.100 and 11.47±0.087μM, respectively. Our results suggest the possibility of developing dual calpain and cathepsin inhibitors by properly modulating structures and/or combining the essential aspects of the functional group effective for specific calpain and cathepsin inhibition.
为了鉴定潜在的钙蛋白酶和组织蛋白酶抑制剂，我们制备了 12 种二氢查尔酮类似物，并测试了它们抑制 μ-钙蛋白酶、m-钙蛋白酶、组织蛋白酶 B 和 L 的能力。在钙蛋白酶抑制试验中，化合物 10 对 m-钙蛋白酶表现出最活跃的抑制活性，IC50 值为 25.25±0.901μM。关于对组织蛋白酶 B 和 L 的抑制，化合物 13 对组织蛋白酶 L 表现出最强的抑制活性，对组织蛋白酶 B 具有中等抑制活性，IC50 值分别为 2.80±0.100 和 11.47±0.087μM。我们的结果表明，通过适当调节结构和/或结合对特定钙蛋白酶和组织蛋白酶抑制有效的功能基团的基本方面，有可能开发双重钙蛋白酶和组织蛋白酶抑制剂。
