acetyl-aspartyl-glutamyl-valyl-aspartal has been researched along with Arterial-Occlusive-Diseases* in 1 studies
1 other study(ies) available for acetyl-aspartyl-glutamyl-valyl-aspartal and Arterial-Occlusive-Diseases
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Design, synthesis, and biological evaluation of isoquinoline-1,3,4-trione derivatives as potent caspase-3 inhibitors.
A series of isoquinoline-1,3,4-trione derivatives were identified as novel and potent inhibitors of caspase-3 through structural modification of the original compound from high-throughput screening. Various analogues (2, 6, 9, 13, and 14) were synthesized and identified as caspase inhibitors, and the introduction of a 6-N-acyl group (compound 13) greatly improved their activity. Some of them showed low nanomolar potency against caspase-3 in vitro (for example, for 6k, IC50 = 40 nM) and significant protection against apoptosis in a model cell system. Additionally, compound 13f demonstrated a dose-dependent decrease in infarct volume in the transient MCA occlusion stroke model. The present small-molecule caspase-3 inhibitor with novel structures different from structures of known caspase inhibitors revealed a new direction for therapeutic strategies directed against diseases involving abnormally up-regulated apoptosis. Topics: Animals; Apoptosis; Arterial Occlusive Diseases; Caspase 3; Caspase Inhibitors; Caspases; Drug Design; Humans; Infarction, Middle Cerebral Artery; Isoquinolines; Jurkat Cells; Male; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Succinates | 2006 |