Cyclic Cystine-Bridged Peptides from the Marine Sponge Clathria basilana Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane

Abstract

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 IC 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.

Bromotryptamine and Bromotyramine Derivatives from the Tropical Southwestern Pacific Sponge Narrabeena nigra

“…The β -carboline moiety has already been found in bryozoans [39] and marine sponges from the genus Hyrtios [40]. The quinolone 15 was previously described in the sponge Clathria basilana and in a bryozoan [41,42], while the kynuramines, as exemplified by 6 , were isolated in an undescribed sponge from the Red Sea [22]. Additionally, the known tryptamine derivatives 9–13 have been found in marine invertebrates such as gorgonians [19], tunicates [20], and different sponges of the genera Ancorina [43], Geodia [21], Jaspis [44], Verongula [15], Hyrtios [14,45], Aplysina [46], but mostly in Smenospongia [16,17,18].…”

Structure–Activity Relationship of Cytotoxic Natural Products from Indonesian Marine Sponges

“…Other cyclopeptides isolated from Clathria basilana , i.e. , microcionamide C ( 83 ), microcionamide D ( 84 ), and microcionamide A ( 85 ), have a disulfide linkage between two cysteine residues, forming a hexapeptide ring (Mokhlesi et al 2017b ). Compounds 83 – 85 exhibit strong cytotoxicity against A2780, leukemia (HL-60, Nomo-1, and Jurkat J16), and lymphoma (Ramos) cell lines.…”

Anticancer Activity of Gukulenin A Isolated from the Marine Sponge Phorbas gukhulensis In Vitro and In Vivo

“…For example, discodermolide, isolated from Discodermia dissolute , induces microtubule-stabilization and inhibits the growth of paclitaxel-resistant ovarian cancer cells [15]. Microcionamides A, C, and D (1–3), cyclic cysteine-bridged peptides isolated from Clathria basilana , showed cytotoxicity in A2780 ovarian cancer cells with IC 50 values ranging from 0.45 μM to 28 μM [16]. Holland et al isolated four new trihydroxysterols from the Australian sponge Psammoclema sp.…”