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Isatin sulfonamide analogs containing a Michael addition acceptor: a new class of caspase 3/7 inhibitors
Wenhua Chu1, Justin Rothfuss, André d'Avignon
1Division of Radiological Sciences, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110, USA.
Abstract:
A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, and have a low potency for inhibiting caspase-1, caspase-6, and caspase-8. The inhibition mechanism was investigated through NMR studies of the reaction between 11d and benzylmercaptan as a model for Cys-285 in the active site of caspase-3.
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