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 |
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Authors: | Roberta Teta Elena Irollo Gerardo Della Sala Giuseppe Pirozzi Alfonso Mangoni Valeria Costantino |
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Institution: | 1.The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, via D. Montesano 49, Napoli 80131, Italy; E-Mails: (R.T.); (G.S.); (A.M.);2.Department of Experimental Oncology, Istituto Nazionale Tumori Fondazione “G. Pascale”, Via M. Semmola, Napoli 80131, Italy; E-Mails: (E.I.); (G.P.) |
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Abstract: | 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. |
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Keywords: | Smenospongia aurea marine natural products peptide/polyketides hybrids structure elucidation antitumor activity |
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