Lyngbyastatins 5-7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp.
Three new analogues of dolastatin 13, termed lyngbyastatins 5-7 ( 1- 3), were isolated from two different collections of marine cyanobacteria, Lyngbya spp., from South Florida. Their planar structures were deduced by a combination of NMR techniques, and the absolute configurations were established by modified Marfey's analysis of the acid hydrolyzates. The related cyclodepsipeptide somamide B ( 4), previously reported from a Fijian cyanobacterium, has also been found in one of the extracts, and its absolute stereochemistry was unambiguously assigned for the first time. Compounds 1- 4 were found to selectively inhibit elastase over several other serine proteases, with IC50 values for porcine pancreatic elastase ranging from 3 to 10 nM.
Taori
Kanchan
K
Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA.
Matthew
Susan
S
Rocca
James R
JR
Paul
Valerie J
VJ
Luesch
Hendrik
H
D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005431:Florida; D006801:Humans; D020128:Inhibitory Concentration 50; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*
D047630:Depsipeptides; D009842:Oligopeptides; C433549:dolastatin 13; C524905:lyngbyastatin 5; C524906:lyngbyastatin 6; C524907:lyngbyastatin 7; C433547:somamide B; D010196:Pancreatic Elastase