The calpains are a conserved family of cysteine proteases that includes several isoforms of which µ–calpain and m-calpain are the most widely distributed in mammalian cells. Calpains have been implicated in normal physiological processes as well as cellular abnormalities such as neurodegenerative disorders, cataract, and cancer. Therefore, calpain inhibitors are of interest as potential therapeutic agents. We have synthesized four new sulfonamide-based peptidomimetic compounds 2-5 as inhibitors of μ-calpain that incorporate (E)-1-(phenyl)-2-phenyldiazene and (E)-1-(phenyl)-2-phenylethene functionalities as the N-terminal capping groups of the inhibitors. Compound 5 with K_i value of 9 nM versus μ-calpain was the most potent member of the group. The compounds were predicted to be more lipophilic compared to MDL28170 based on CLogP estimation. They displayed moderate to good antiproliferative activity versus melanoma cell lines (A-375 and B-16F1) and PC-3 prostate cancer cells in vitro. Additionally, one member of the group (compound 3) inhibited DU-145 cell invasion by 80% at 2 μM concentration in the Matrigel cell invasion assay.

钙蛋白酶是一个半胱氨酸蛋白酶的保守家族，其中包括几种同工型，其中μ–calpain和m-calpain在哺乳动物细胞中分布最广。钙蛋白酶已牵涉到正常的生理过程以及细胞异常，例如神经退行性疾病，白内障和癌症。因此，钙蛋白酶抑制剂作为潜在的治疗剂是令人感兴趣的。我们已合成了四个新基于磺酰胺的拟肽化合物2 - 5为μ钙蛋白酶掺入抑制剂（ë）-1-（苯基）-2- phenyldiazene和（ë）-1-（苯基）-2- phenylethene功能如抑制剂的N末端封端基团。化合物5与相对于μ-钙蛋白酶，K _i值为9 nM是该组中最有力的成员。根据CLogP估计，与MDL28170相比，预测该化合物具有更高的亲脂性。与体外黑色素瘤细胞系（A-375和B-16F1）和PC-3前列腺癌细胞相比，它们具有中等至良好的抗增殖活性。另外，在Matrigel细胞侵袭测定中，该组中的一个成员（化合物3）以2μM的浓度抑制了DU-145细胞侵袭80％。