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