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.
The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, via D. Montesano 49, Napoli 80131, Italy. valeria.costantino@unina.it.
Roberta
R
Teta
Elena
E
Irollo
Gerardo
G
Della Sala
Giuseppe
G
Pirozzi
Alfonso
A
Mangoni
Valeria
V
Costantino
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D017691:Caribbean Region; D045744:Cell Line, Tumor; D000458:Cyanobacteria / Q000235:genetics / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D054879:Halogenation; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D061065:Polyketides / Q000737:chemistry* / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry* / Q000382:microbiology; D012336:RNA, Ribosomal, 16S / Q000235:genetics
D000970:Antineoplastic Agents; D010455:Peptides; D061065:Polyketides; D012336:RNA, Ribosomal, 16S