Largamides A–C, Tiglic Acid-Containing Cyclodepsipeptides with Elastase-Inhibitory Activity from the Marine Cyanobacterium Lyngbya confervoides

Abstract

Three unusual tiglic acid-containing cyclodepsipeptides, possessing the revised regioisomeric structures for largamides A – C (1–3), have been isolated from the marine cyanobacterium Lyngbya confervoides collected from southeastern Florida. The two-dimensional structures were determined by NMR spectroscopy and the absolute configurations by chiral HPLC analysis of degradation products. Compounds 1–3 are moderate inhibitors of mammalian elastase activity in vitro with IC₅₀ values ranging from 0.53 to 1.41 µM.

Key words

marine cyanobacteria - Lyngbya confervoides - cyclodepsipeptides - elastase

References

• 1 Gerwick W H, Tan L T, Sitachitta N. Nitrogen-containing metabolites from marine cyanobacteria.  Alkaloids Chem Biol. 2001;  57 75-184
• 2 Welker M, von Döhren H. Cyanobacterial peptides – nature's own combinatorial biosynthesis.  FEMS Microbiol Rev. 2006;  30 530-563
• 3 Matthew S, Ross C, Rocca J R, Paul V J, Luesch H. Lyngbyastatin 4, a dolastatin 13 analogue with elastase and chymotrypsin inhibitory activity from the marine cyanobacterium Lyngbya confervoides.  J Nat Prod. 2007;  70 124-127
• 4 Taori K, Matthew S, Rocca J R, Paul V J, Luesch H. Lyngbyastatins 5–7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp.  J Nat Prod. 2007;  70 1593-1600
• 5 Matthew S, Ross C, Paul V J, Luesch H. Pompanopeptins A and B, new cyclic peptides from the marine cyanobacterium Lyngbya confervoides.  Tetrahedron. 2008;  64 4081-4089
• 6 Plaza A, Bewley C A. Largamides A – H, unusual cyclic peptides from the marine cyanobacterium Oscillatoria sp.  J Org Chem. 2006;  71 6898-6907
• 7 Houghton A M, Quintero P A, Perkins D L, Kobayashi D K, Kelley D G, Marconcini L A, Mecham R P, Senior R M, Shapiro S D. Elastin fragments drive disease progression in a murine model of emphysema.  J Clin Invest. 2006;  116 753-759
• 8 Paul V J, Thacker R W, Banks K, Golubic S. Benthic cyanobacterial bloom impacts the reefs of South Florida (Broward County, USA).  Coral Reefs. 2005;  24 693-697
• 9 Shiomi K, Haneda K, Tomoda H, Iwai Y, Omura S. Cytosaminomycins, new anticoccidial agents produced by Streptomyces sp. KO-8119. II. Structure elucidation of cytosaminomycins A, B, C and D.  J Antibiot (Tokyo). 1994;  47 782-786
• 10 Mann J. Secondary metabolism. 2nd edition. Oxford; Clarendon Press 1987: 95-172
• 11 Rhee S W, Leete E, McGaw B A. Stereospecificity of enzymic dehydrogenation during tiglate biosynthesis.  J Am Chem Soc. 1980;  102 7344-7348
• 12 Rennert B, Melzig M F. Free fatty acids inhibit the activity of Clostridium histolyticum collagenase and human neutrophil elastase.  Planta Med. 2002;  68 767-769