Susan Matthew

Apratoxin E, a Cytotoxic Peptolide from a Guamanian Collection of the Marine Cyanobacterium Lyngbya bouillonii

A collection of the marine cyanobacterium Lyngbya bouillonii from Guam afforded apratoxin E (1), a new peptide-polyketide hybrid of the apratoxin class of cytotoxins. The planar structure of 1 was elucidated by NMR spectroscopic analysis and mass spectrometry. Configurational assignments of stereocenters in the peptide portion were made by chiral HPLC analysis of the acid hydrolysate. The relative configuration in the polyketide moiety was assigned by comparison of NMR data including proton-proton coupling constants with those of the known analogues. Apratoxin E (1) displayed strong cytotoxicity against several cancer cell lines derived from colon, cervix, and bone, ranging from 21 to 72 nM, suggesting that the alpha,beta-unsaturation of the modified cysteine residue is not essential for apratoxin activity. The 5- to 15-fold reduced activity compared with apratoxin A (2) is attributed to the dehydration in the long-chain polyketide unit, which could affect the conformation of the molecule.

Cytotoxic Halogenated Macrolides and Modified Peptides from the Apratoxin-Producing Marine Cyanobacterium Lyngbya bouillonii from Guam

Collections of the marine cyanobacterium Lyngbya bouillonii from shallow patch reefs in Apra Harbor, Guam, afforded three hitherto undescribed analogues of the glycosidic macrolide lyngbyaloside, namely, 2-epi-lyngbyaloside (1) and the regioisomeric 18E- and 18Z-lyngbyalosides C (2 and 3). Concurrently we discovered two new analogues of the cytoskeletal actin-disrupting lyngbyabellins, 27-deoxylyngbyabellin A (4) and lyngbyabellin J (5), a novel macrolide of the laingolide family, laingolide B (6), and a linear modified peptide, lyngbyapeptin D (7), along with known lyngbyabellins A and B, lyngbyapeptin A, and lyngbyaloside. The structures of 1-7 were elucidated by a combination of NMR spectroscopic and mass spectrometric analysis. Compounds 1-6 were either brominated (1-3) or chlorinated (4-6), consistent with halogenation being a hallmark of many marine natural products. All extracts derived from these L. bouillonii collections were highly cytotoxic due to the presence of apratoxin A or apratoxin C. Compounds 1-5 showed weak to moderate cytotoxicity to HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells.

Phylogenetic and Chemical Diversity of Three Chemotypes of Bloom-Forming Lyngbya Species (Cyanobacteria: Oscillatoriales) from Reefs of Southeastern Florida

ABSTRACT The cyanobacterial genus Lyngbya includes free-living, benthic, filamentous cyanobacteria that form periodic nuisance blooms in lagoons, reefs, and estuaries. Lyngbya spp. are prolific producers of biologically active compounds that deter grazers and help blooms persist in the marine environment. Here, our investigations reveal the presence of three distinct Lyngbya species on nearshore reefs in Broward County, FL, sampled in 2006 and 2007. With a combination of morphological measurements, molecular biology techniques, and natural products chemistry, we associated these three Lyngbya species with three distinct Lyngbya chemotypes. One species, identified as Lyngbya cf. confervoides via morphological measurements and 16S rRNA gene sequencing, produces a diverse array of bioactive peptides and depsipeptides. Our results indicate that the other two Lyngbya species produce either microcolins A and B or curacin D and dragonamides C and D. Results from screening for the biosynthetic capacity for curacin production among the three Lyngbya chemotypes in this study correlated that capacity with the presence of curacin D. Our work on these bloom-forming Lyngbya species emphasizes the significant phylogenetic and chemical diversity of the marine cyanobacteria on southern Florida reefs and identifies some of the genetic components of those differences.

Dragonamides C and D, linear lipopeptides from the marine cyanobacterium brown Lyngbya polychroa.

Two new linear lipopeptides, 1 and 2, and a known compound, curacin D, have been isolated from a marine cyanobacterium, brown Lyngbya polychroa, collected from Hollywood Beach, Fort Lauderdale, Florida. Their planar structures were elucidated by 1D and 2D NMR techniques, and absolute configurations were assigned using chiral HPLC. The new compounds were assigned the trivial names dragonamide C (1) and dragonamide D (2), as their peptide moiety is related to previously reported dragonamides A and B.

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

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 IC(50) values ranging from 0.53 to 1.41 microM.

Tiglicamides A―C, cyclodepsipeptides from the marine cyanobacterium Lyngbya confervoides

The Floridian marine cyanobacterium Lyngbya confervoides afforded cyclodepsipeptides, termed tiglicamides A-C (1-3), along with their previously reported analogues largamides A-C (4-6), all of which possess an unusual tiglic acid moiety. Their structures were deduced by one- and two-dimensional NMR combined with mass spectrometry and the absolute configurations established by chiral HPLC and Marfeys analysis of the degradation products. Compounds 1-3 moderately inhibited porcine pancreatic elastase in vitro with IC(50) values from 2.14 to 7.28 microM. Compounds 1-6 differ from each other by one amino acid residue within the cyclic core structure, suggesting an unusually relaxed substrate specificity of the nonribosomal peptide synthetase that is the putative biosynthetic enzyme responsible for the corresponding amino acid incorporation.

Intramolecular Modulation of Serine Protease Inhibitor Activity in a Marine Cyanobacterium with Antifeedant Properties

Extracts of the Floridian marine cyanobacterium Lyngbya cf. confervoides were found to deter feeding by reef fish and sea urchins (Diadema antillarum). This antifeedant activity may be a reflection of the secondary metabolite content, known to be comprised of many serine protease inhibitors. Further chemical and NMR spectroscopic investigation led us to isolate and structurally characterize a new serine protease inhibitor 1 that is formally derived from an intramolecular condensation of largamide D (2). The cyclization resulted in diminished activity, but to different extents against two serine proteases tested. This finding suggests that cyanobacteria can endogenously modulate the activity of their protease inhibitors.

Bioassay-guided isolation and identification of desacetylmicrocolin B from Lyngbya cf. polychroa.

Bioassay-guided fractionation of a non-polar extract of Lyngbya cf. polychroa resulted in the isolation of the cytotoxic desacetylmicrocolin B (1) as well as the known compounds microcolins A (2) and B (3). Compound 1 was found to inhibit the growth of HT-29 colorectal adenocarcinoma and IMR-32 neuroblastoma cells with half maximal inhibitory concentration (IC(50)) values of 14 nM for both cancer cell types. Microcolins A and B were found to have little activity against two strains of the marine fungus Dendryphiella salina with LD(50) values above 200 microg/mL. Compounds 1, 2, and 3 were obtained by reverse-phase chromatography and their structures were determined by NMR and MS. In this paper we report the isolation, identification, and biological activity of 1.

Ellagic acid glycosides from Turpinia ternata

Bioassay-guided fractionation of the methanolic extract of Turpinia ternata stems, has led to the isolation of the new ellagic acid derivative 3,4′-di-O-methylellagic acid-4-O-α-L-arabinofuranoside (1), and the known compounds ellagic acid (2), 3-O-methyl ellagic acid (3), 3-O-methylellagic acid-3′-O-α-L-rhamnopyranoside (4), and 3,3′-di-O-methylellagic acid-4′-O-α-D-glucopyranoside (5). Their structures were elucidated by extensive spectroscopic methods. Compounds 1, 3, and 4 showed moderate antioxidant activity against DPPH free radical, whereas compound 1 was found to be moderately cytotoxic against Artemia salina larvae.

A new C9 nor-isoprenoid glucoside from Rantherium suaveolens.

The new C9 nor-isoprenoid 3-methyl-octa-1,5-diene-7-one-3-O-β-D-glucopyranoside, named as ranthenone glucoside (1), together with the previously known 9-hydoxylinaloyl glucoside (2), sitosterol-3β-O-[6′-palmitoyl-β-D-glucopyranoside] (3), scopoletin (4), fraxetin (5), and scopolin (6), were isolated from the aerial parts of Rantherium suaveolens. The structures of these compounds were elucidated by extensive spectroscopic analysis.