Chu Wenhua, Zhang Jun, Zeng Chenbo, Rothfuss Justin, Tu Zhude, Chu Yunxiang, Reichert David E, Welch Michael J, Mach Robert H
Division of Radiological Sciences, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110, USA.
J Med Chem. 2005 Dec 1;48(24):7637-47. doi: 10.1021/jm0506625.
A number of isatin sulfonamide analogues were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated in vitro. Several compounds displaying a nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, were identified. These compounds were also observed to have a low potency for inhibiting the initiator caspases, caspase-1 and caspase-8, and caspase-6. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The results of the current study revealed a number of non-peptide-based caspase inhibitors that may be useful in assessing the role of inhibiting the executioner caspases in minimizing tissue damage in disease conditions characterized by unregulated apoptosis.
制备了多种异吲哚酮磺酰胺类似物，并在体外评估了它们对caspase-1、-3、-6、-7和-8的抑制效力。鉴定出了几种对刽子手半胱天冬酶caspase-3和caspase-7具有纳摩尔抑制效力的化合物。还观察到这些化合物对起始半胱天冬酶caspase-1、caspase-8和caspase-6的抑制效力较低。分子模拟研究进一步深入了解了这类化合物与活化的caspase-3之间的相互作用。当前研究结果揭示了一些非肽类半胱天冬酶抑制剂，它们可能有助于评估在以不受调控的细胞凋亡为特征的疾病状态下，抑制刽子手半胱天冬酶在最小化组织损伤中的作用。
