Smenamides A and B, Chlorinated Peptide/Polyketide Hybrids Containing a Dolapyrrolidinone Unit from the Caribbean Sponge Smenospongia aurea. Evaluation of Their Role as Leads in Antitumor Drug Research

An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS and homo- and heteronuclear 2D NMR experiments. Structures of smenamides suggested that they are products of the cyanobacterial metabolism, and 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea. Smenamides showed potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, which for compound 1 is exerted through a clear pro-apoptotic mechanism. This makes smenamides promising leads for antitumor drug design.

[1]  R. Hoffman.  Structure Determination of Organic Compounds , 2005 .

[2]  D. Newman,et al.  Natural products as leads to antitumor drugs , 2013, Phytochemistry Reviews.

[3]  Hollenbeak Kh,et al.  Aplysinopsin: antineoplastic tryptophan derivative from the marine sponge Verongia spengelii. , 1977 .

[4]  G. Cirino,et al.  Tedanol: a potent anti-inflammatory ent-pimarane diterpene from the Caribbean Sponge Tedania ignis. , 2009, Bioorganic & medicinal chemistry.

[5]  Ultrastructure, Molecular Phylogenetics, and Chlorophyll a Content of Novel Cyanobacterial Symbionts in Temperate Sponges , 2012, Microbial Ecology.

[6]  E. Fattorusso,et al.  A New Antibiotic Chloro-Sesquiterpene from the Caribbean Sponge Smenospongia aurea , 1993 .

[7]  Moriya Ohkuma,et al.  Defensive Bacteriome Symbiont with a Drastically Reduced Genome , 2013, Current Biology.

[8]  D. Stierle,et al.  Some metabolites of the marine sponges Smenospongia aurea and Smenospongia (.ident.Polyfibrospongia) echina , 1980 .

[9]  Kenneth B. Tomer,et al.  The isolation and structure of a remarkable marine animal antineoplastic constituent: dolastatin 10 , 1987 .

[10]  W. Gerwick,et al.  Belamide A, a new antimitotic tetrapeptide from a Panamanian marine cyanobacterium , 2006 .

[11]  A. Wilmotte,et al.  Testing of primers for the study of cyanobacterial molecular diversity by DGGE. , 2006, Journal of microbiological methods.

[12]  K. Oh,et al.  Scalarane sesterterpenes from the sponge Smenospongia sp. , 2008, Journal of natural products.

[13]  D. Białońska,et al.  Aplysinopsins - Marine Indole Alkaloids: Chemistry, Bioactivity and Ecological Significance , 2009, Marine drugs.

[14]  E. Ghisalberti.  Bioactive Tetramic Acid Metabolites , 2003 .

[15]  William H Gerwick,et al.  Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. , 2004, Chemistry & biology.

[16]  R. Quinn,et al.  Aplysinopsin, a new tryptophan derivative from a sponge , 1977 .

[17]  M. Bourguet-Kondracki,et al.  Smenoqualone a novel sesquiterpenoid from the marine sponge Smenospongia sp. , 1992 .

[18]  S. Matsunaga,et al.  Mycapolyols A-F, new cytotoxic metabolites of mixed biogenesis from the marine sponge Mycale izuensis. , 2005, Organic letters.

[19]  R. Kiss,et al.  Evaluation of the antiproliferative activity of diterpene isonitriles from the sponge Pseudoaxinella flava in apoptosis-sensitive and apoptosis-resistant cancer cell lines. , 2011, Journal of natural products.

[20]  C. Mahidol,et al.  Iodo–sesquiterpene hydroquinone and brominated indole alkaloids from the Thai sponge Smenospongia sp. , 2012 .

[21]  Y. Choi,et al.  Metabolomics for the rapid dereplication of bioactive compounds from natural sources , 2013, Phytochemistry Reviews.

[22]  J. Panamá,et al.  Cryptic diversity of the symbiotic cyanobacterium Synechococcus spongiarum among sponge hosts , 2008 .

[23]  R. Cerny,et al.  Isolation and Structure of the Cytostatic Linear Depsipeptide Dolastatin 15 , 1989 .