Smenamides A and B

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Figure 1. Structures of smenamide A (1) and B (2).

 Smenamide A (1)
 The positive ion mode high-resolution ESI mass spectrum of smenamide A (1)  displayed [M + H]⁺ and [M + Na]⁺ pseudomolecular ion peak at m/z 501.2508 and 523.2326, respectively. Both ions showed intense (32%) M + 2 isotope peaks, suggesting the presence of one atom of chlorine, and were indicative of the molecular formula C₂₈H₃₇ClN₂O₄ (calcd. 501.2515 for C₂₈H₃₈ClN₂O₄ and 523.2334 for C₂₈H₃₇ClN₂O₄Na). The peak at m/z 487.2557 ([M − HCl + Na]⁺) in the HRMS/MS spectrum confirmed the presence of chlorine in the molecule.


 Table 1. NMR data of smenamide A (1) (700 MHz, CD₃OD).
Click here to display table

Smenamide A (1)

Colorless amorphous solid, HRESIMS (positive ion mode, MeOH) m/z 523.2326 ([M + Na]⁺, C₂₈H₃₇ClN₂O₄Na⁺, calcd. 532.2334), m/z 501.2509 ([M + Na]⁺, C₂₈H₃₈ClN₂O₄⁺, calcd. 501.2515); MS isotope pattern: M (100%), M + 1 (32%, calcd. 31.5%), M + 2 (37%, calcd. 36.0%), M + 3 (10%, calcd. 10.6%,); HRESIMS/MS (parent ion m/z 523.23, C₂₈H₃₇ClN₂O₄Na⁺): m/z 487.2557 (C₂₈H₃₆N₂O₄Na⁺, calcd. 487.2567), 397.2092 (C₂₁H₃₀N₂O₄Na⁺, calcd. 397.2098), 320.1384 (C₁₆H₂₄ClNO₂Na⁺, calcd. 320.1388), 284.1618 (C₁₆H₂₃NO₂Na⁺, calcd. 284.1621), 244.0941 (C₁₂H₁₅NO₃Na⁺, calcd. 244.0944), 226.0836 (C₁₂H₁₃NO₂Na⁺, calcd. 226.0838), 202.0472 (C₉H₉NO₃Na⁺, calcd. 226.0475); ¹H and ¹³C NMR: Table 1; UV (MeOH): λ_max(ε) 287 nm (8200), 246 nm (46000), 225 nm (92000); CD (MeOH): λ_max(Δε) 238 (+33), 219 (−30).

Smenamide B (2)

Colorless amorphous solid, HRESIMS (positive ion mode, MeOH) m/z 523.2320 ([M + Na]⁺, calcd. for C₂₈H₃₇ClN₂O₄Na⁺ 532.2334), m/z 501.2505 ([M + Na]⁺, calcd. for C₂₈H₃₈ClN₂O₄⁺ 501.2515); MS isotope pattern: M (100%), M + 1 (31%, calcd. 31.5%), M + 2 (36%, calcd. 36.0%), M + 3 (11%, calcd. 10.6%,); HRESIMS/MS (parent ion m/z 523.23, C₂₈H₃₇ClN₂O₄Na⁺): m/z 487.25567 (C₂₈H₃₆N₂O₄Na⁺, calcd. 487.2567), 397.2091 (C₂₁H₃₀N₂O₄Na⁺, calcd. 397.2098), 320.1383 (C₁₆H₂₄ClNO₂Na⁺, calcd. 320.1388), 284.1617 (C₁₆H₂₃NO₂Na⁺, calcd. 284.1621), 244.0941 (C₁₂H₁₅NO₃Na⁺, calcd. 244.0944), 226.0835 (C₁₂H₁₃NO₂Na⁺, calcd. 226.0838), 202.0471 (C₉H₉NO₃Na⁺, calcd. 226.0475); ¹H and ¹³C NMR: Table 1; ¹H and ¹³C NMR: Supplementary Table S1; UV (MeOH): λ_max(ε) 287 nm (15000), 248 nm (42000), 225 nm (84000); CD (MeOH): λ_max(Δε) 237 (+7.3).

Mar. Drugs 2013, 11(11), 4451-4463; doi:10.3390/md11114451

Article.......http://www.mdpi.com/1660-3397/11/11/4451/htm

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

Roberta Teta ¹, Elena Irollo ², Gerardo Della Sala ¹, Giuseppe Pirozzi ², Alfonso Mangoni ¹ and Valeria Costantino ^1,*

¹The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, via D. Montesano 49, Napoli 80131, Italy; E-Mails: roberta.teta@unina.it (R.T.); gerardo.dellasala@unina.it (G.S.); alfonso.mangoni@unina.it (A.M.)

²Department of Experimental Oncology, Istituto Nazionale Tumori Fondazione “G. Pascale”, Via M. Semmola, Napoli 80131, Italy; E-Mails: e.irollo@istitutotumori.na.it (E.I.); g.pirozzi@istitutotumori.na.it (G.P.)

*Author to whom correspondence should be addressed; E-Mail: valeria.costantino@unina.it; Tel.: +39-081-678-504; Fax: +39-081-678-552.

Received: 27 September 2013; in revised form: 25 October 2013 / Accepted: 25 October 2013 /
Published: 8 November 2013

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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