title: Isatin sulfonamide analogs containing a Michael addition acceptor: a new class of caspase 3/7 inhibitors.
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.
authors.affiliation: Division of Radiological Sciences, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110, USA.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Chu
authors.forename: Justin
authors.initials: J
authors.lastname: Rothfuss
authors.forename: André
authors.initials: A
authors.lastname: d'Avignon
authors.forename: Chenbo
authors.initials: C
authors.lastname: Zeng
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hotchkiss
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
mesh_terms: D061945:Caspase Inhibitors; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D061945:Caspase Inhibitors; D013449:Sulfonamides; D007510:Isatin