Nam Dong Hyuk, Lee Kwang Seob, Kim Sang Hoon, Kim Sung Min, Jung Seo Yun, Chung Sung Hyun, Kim Hyoung Ja, Kim Nam Doo, Jin Changbae, Lee Yong Sup
Department of Pharmaceutical Sciences, Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Bioorg Med Chem Lett. 2008 Jan 1;18(1):205-9. doi: 10.1016/j.bmcl.2007.10.097. Epub 2007 Oct 30.
Calpains are involved in a variety of calcium-regulated cellular processes, such as signal transduction, cell proliferation, differentiation, and apoptosis. Excessive calpain activation contributes to serious cellular damage and has been reported in many pathological conditions. 4-Quinolinone 2-carboxamide derivatives were prepared and evaluated for mu-calpain inhibitory activities. Of the compounds synthesized, 3a and 3k, which possess a primary amide and 4-methoxyphenethyl amide at P1' region, were found to most potently inhibit mu-calpain with IC50 values of 0.71+/-0.07 and 0.73+/-0.23 microM, respectively. On the other hand, the incorporation of pyridine-containing amides decreased inhibitory activity.
钙蛋白酶参与多种钙调节的细胞过程，如信号转导、细胞增殖、分化和凋亡。钙蛋白酶的过度激活会导致严重的细胞损伤，并且在许多病理状况中都有报道。制备了4-喹啉酮-2-甲酰胺衍生物并评估其对微钙蛋白酶的抑制活性。在合成的化合物中，在P1'区域具有伯酰胺和4-甲氧基苯乙酰胺的3a和3k被发现对微钙蛋白酶具有最强的抑制作用，IC50值分别为0.71±0.07和0.73±0.23微摩尔。另一方面，含吡啶酰胺的引入降低了抑制活性。
