This title appears in the Scientific Report :
2018
Please use the identifier:
http://dx.doi.org/10.1021/acs.jnatprod.7b00477 in citations.
Cyclic Cystine-Bridged Peptides from the Marine Sponge Clathria basilana Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane
Cyclic Cystine-Bridged Peptides from the Marine Sponge Clathria basilana Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane
Investigation of the sponge Clathria basilana collected in Indonesia afforded five new peptides, including microcionamides C (1) and D (2), gombamides B (4), C (5), and D (6), and an unusual amide, (E)-2-amino-3-methyl-N-styrylbutanamide (7), along with 11 known compounds, among them microcionamide...
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Personal Name(s): | Mokhlesi, Amin |
---|---|
Stuhldreier, Fabian / Wex, Katharina W. / Berscheid, Anne / Hartmann, Rudolf / Rehberg, Nidja / Sureechatchaiyan, Parichat / Chaidir, Chaidir / Kassack, Matthias / Kalscheuer, Rainer / Brötz-Oesterhelt, Heike / Wesselborg, Sebastian / Stork, Björn / Daletos, Georgios (Corresponding author) / Proksch, Peter (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | Journal of natural products, 80 (2017) 11, S. 2941–2952 |
Imprint: |
Washington, DC
Soc.
2017
|
DOI: |
10.1021/acs.jnatprod.7b00477 |
PubMed ID: |
29094598 |
Document Type: |
Journal Article |
Research Program: |
Functional Macromolecules and Complexes |
Publikationsportal JuSER |
Investigation of the sponge Clathria basilana collected in Indonesia afforded five new peptides, including microcionamides C (1) and D (2), gombamides B (4), C (5), and D (6), and an unusual amide, (E)-2-amino-3-methyl-N-styrylbutanamide (7), along with 11 known compounds, among them microcionamide A (3). The structures of the new compounds were elucidated by one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of the constituent amino acid residues in 1–7 were determined by Marfey’s analysis. Microcionamides A, C, and D (1–3) showed in vitro cytotoxicity against lymphoma (Ramos) and leukemia cell lines (HL-60, Nomo-1, Jurkat J16), as well as against a human ovarian carcinoma cell line (A2780) with IC50 values ranging from 0.45 to 28 μM. Mechanistic studies showed that compounds 1–3 rapidly induce apoptotic cell death in Jurkat J16 and Ramos cells and that 1 and 2 potently block autophagy upon starvation conditions, thereby impairing pro-survival signaling of cancer cells. In addition, microcionamides C and A (1 and 3) inhibited bacterial growth of Staphylococcus aureus and Enterococcus faecium with minimal inhibitory concentrations between 6.2 and 12 μM. Mechanistic studies indicate dissipation of the bacterial membrane potential. |