title: N-benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: synthesis, in vitro activity, and molecular modeling studies.
abstract: 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.
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: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Chenbo
authors.initials: C
authors.lastname: Zeng
authors.forename: Justin
authors.initials: J
authors.lastname: Rothfuss
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Chu
authors.forename: David E
authors.initials: DE
authors.lastname: Reichert
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
mesh_terms: D017209:Apoptosis; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000737:chemistry*; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001593:Benzyl Compounds; D061945:Caspase Inhibitors; D013449:Sulfonamides; D007510:Isatin; D053148:Caspase 3; D020169:Caspases