New Peptolides from the Cyanobacterium Nostoc insulare as Selective and Potent Inhibitors of Human Leukocyte Elastase

Eight new cyanopeptolins (insulapeptolides A-H) were obtained from the cyanobacterium Nostoc insulare. Their isolation was guided by their bioactivity toward the target enzyme human leukocyte elastase, molecular biological investigations, and MALDI-TOF analysis. These peptides are selective inhibitors of human leukocyte elastase with activities in the nanomolar range. Insulapeptolide D (4) was the most potent compound with an IC50 value of 85 nM (K-i value of 36 nM).