Caspase inhibitors - A chemist's perspective

Contribution of apoptotic mechanisms to neurodegeneration is an emerging co ncept. Caspases which are activated during apoptotic cell death may serve a s an attractive target of pharmacological intervention. Caspase inhibitors include proteins, peptides, peptidomimetics and various small molecules. Pe ptide conjugates with quinones, epoxyquinones and epoxyquinols which consti tute new types of pharmaeophores exhibit submicromolar activity against cas pase-3 and show moderate neuroprotective effects on neuronal cells. Peptide -derived inhibitors may suffer from insufficient cell membrane permeability . However, double eater-type prodrugs may offer an option to transport a pe ptide-like inhibitor across the cell membrane. These developments may lead to identification of novel neuroprotective drugs.