Depsipeptides from a Guamanian marine cyanobacterium, Lyngbya bouillonii, with selective inhibition of serine proteases

Abstract

Bouillomides A (1) and B (2) are two depsipeptide analogues of dolastatin 13. Isolated from a Guamanian sample of Lyngbya bouillonii, the planar structures were elucidated on the basis of HR-ESI-MS and NMR data, while the absolute configurations were determined by employing functional group conversions, modified Marfey’s analysis, and detailed analyses of ROESY correlations. Compounds 1 and 2 selectively inhibited serine proteases elastase (IC50 = 1.9 μM for both) and chymotrypsin (IC50 = 0.17 and 9.3 μM, respectively) while showing no inhibition of trypsin (IC50 > 100 μM).

Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii

“…genomes, on average [ 8 , 9 , 10 ]. Consistent with this finding, some 70 different isolated and structurally defined compounds have been reported from M. bouillonii ( Table S1 ) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. These display a broad structural diversity, and include peptides [ 41 ], cyclodepsipeptides [ 16 ], macrolides [ 12 ] and glycosidic macrolides [ 35 ], and lipids [ 43 ].…”

“…M. bouillonii has a wide distribution across the tropical Western Pacific and Indian Oceans. However, M. bouillonii metabolites have only been described from collections made from a limited number of discrete locations, including Papua New Guinea [ 14 , 19 , 23 , 25 , 28 , 33 , 34 , 35 , 39 , 41 , 43 ], Guam [ 11 , 12 , 15 , 16 , 18 , 20 , 22 , 24 , 29 , 36 , 37 , 42 ], Palau [ 11 , 18 , 38 , 40 , 44 ], Malaysia [ 26 , 27 ], Palmyra Atoll [ 13 , 21 ], Fiji [ 31 ] (The organism in this manuscript is reported as M. producens , however the manuscript includes a photo of the organism, which displays a morphology characteristic of shrimp-woven M. bouillonii . The 16S rRNA gene-based classification was inconclusive and known compounds previously isolated from M. bouillonii were reported.…”

“…Orthogonally, it has become a common strategy to look in underexplored geographical locations in order to find new and unique natural products. This has led natural products discovery efforts to interesting and exotic habitats, including tropical coral reefs [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], hypersaline lakes [ 54 ], the Arctic [ 55 ] and Antarctic [ 56 ], hydrothermal vents [ 57 ], and the deep sea [ 58 ]. In spite of the acknowledgement that sampling in new geographical locations can allow access to new natural products, there are few examples of systematically applying geographical knowledge in order to inform natural product discovery.…”

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

“…In contrast, although a pharmacological activity was described, and an IC 50 for inhibition of an enzyme or receptor determined, detailed molecular mechanism of action studies were unavailable at the time of publication for the following 47 marine compounds included in Table 3: alotaketals A and B ( 183 , 184 ) [166]; aquastatin A ( 185 ) [167]; australin E ( 186 ) [168]; lyngbyastatins 9 & 10 ( 187 , 188 ) [169]; brunsvicamides A, B and C ( 189 – 191 ) [170]; carteriosulfonic acids A, B and C ( 192 – 194 ) [171]; Carteriospongia foliascens sesterterpenoids ( 195 , 196 ) [172]; clavatadines D and E ( 197 , 198 ) [173]; fibrosterol sulfates A and B ( 199 , 200 ) [174]; gracilin L ( 201 ) [175]; grassystatins A, B and C ( 141 – 143 ) [133]; 2-hydroxycircumdatin C ( 202 ) [176]; jaspaquinol ( 203 ) [177]; largamides A, B and C ( 204 – 206 ) [178]; largamide D oxazolidine ( 207 ) [179]; Laurencia similis brominated metabolites ( 208 , 209 ) [180]; molassamide ( 210 ) [181]; myrothenone A ( 211 ) [182]; 42-hydroxy-palytoxin ( 212 ) [183]; plectosphaeroic acids A, B and C ( 213 – 215 ) [184]; puupehenone ( 216 ) [177]; Sinularia numerosa oxylipin ( 217 ) [185]; sipholenone E ( 218 ) [186]; spartinoxide ( 219 ) [187]; 23- nor -spiculoic acid B ( 220 ) [188]; tanikolide dimer ( 221 ) [189]; tamulamides A and B ( 222 , 223 ) [190]; terretonins E and F ( 224 , 225 ) [191]; and tetrangulol methyl ether ( 226 ) [192]. …”

α,β-Dehydroamino acids in naturally occurring peptides

“…Dolastatin 13 (sea hare Dolabella auricularia ) (Pettit et al 1989 ), symplostatin 2 (cyanobacteria Symploca hydnoides ) (Harrigan et al 1999 ), somamides (cyanobacteria Schizothrix and Lyngbya majuscula ) (Nogle et al 2001 ), lyngbyastatins 4-10 (cyanobacteria Lyngbya confervoides and semiplena ) (Matthew et al 2007 ; Taori et al 2007 ; Kwan et al 2009 ), bouillomides (cyanobacteria Lyngbya bouillonii ) (Rubio et al 2010 ), and molassamides B (cyanobacteria Dichothrix utahensis ) (Gunasekera et al 2010 ) can also be perceived as a family of compounds 10 . These cyclodepsipentapeptides contain ( Z )-ΔAbu residue with C-terminal 3-amino-6-hydroxy-2-piperidone (Ahp).…”