TY  - JOUR
AU  - Mokhlesi, Amin
AU  - Stuhldreier, Fabian
AU  - Wex, Katharina W.
AU  - Berscheid, Anne
AU  - Hartmann, Rudolf
AU  - Rehberg, Nidja
AU  - Sureechatchaiyan, Parichat
AU  - Chaidir, Chaidir
AU  - Kassack, Matthias
AU  - Kalscheuer, Rainer
AU  - Brötz-Oesterhelt, Heike
AU  - Wesselborg, Sebastian
AU  - Stork, Björn
AU  - Daletos, Georgios
AU  - Proksch, Peter
TI  - Cyclic Cystine-Bridged Peptides from the Marine Sponge Clathria basilana Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane
JO  - Journal of natural products
VL  - 80
IS  - 11
SN  - 0163-3864
CY  - Washington, DC
PB  - Soc.
M1  - FZJ-2017-08598
SP  - 2941–2952
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29094598
UR  - <Go to ISI:>//WOS:000416500400011
DO  - DOI:10.1021/acs.jnatprod.7b00477
UR  - https://juser.fz-juelich.de/record/841560
ER  -