N-benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: Synthesis, in vitro activity, and molecular modeling studies

Wenhua Chu, Jun Zhang, Chenbo Zeng, Justin Rothfuss, Zhude Tu, Yunxiang Chu, David E. Reichert, Michael J. Welch, Robert H. Mach

Research output: Contribution to journalArticle

96 Scopus citations

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.

Original languageEnglish
Pages (from-to)7637-7647
Number of pages11
JournalJournal of Medicinal Chemistry
Volume48
Issue number24
DOIs
StatePublished - Dec 1 2005

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