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One novel brominated nocardiopsistin D (1) and two new sulfur-containing nocardiopsistins E–F (2–3) were identified from Nocardiopsissp. HB-J378. The biosynthetic gene cluster ncdfeaturing a brominase was identified. Compounds 1–3exhibited significant anti-methicillin-resistant Staphylococcus aureus(anti-MRSA) activities with minimum inhibitory concentrations (MICs) of 0.098, 3.125, and 0.195 μg/mL, respectively. The single bromination in 1drastically enhanced the anti-MRSA activity by 128-fold without altering cell toxicity and acquired new activities against the bacterial pathogens vancomycin-resistant S. aureus(VRSA), Enterococcus faecium, and Bacillus cereus.

Two new indolo[3,2-a]carbazoles (1, 2) were isolated from a deep-water collection of a sponge of the genus Asteropus. The structures of 1and 2were determined through the analysis of spectroscopic data including mass spectrometry and 2D-NMR. Compound 1showed minimum inhibitory concentrations of 25 μg/mL against the fungal pathogen Candida albicansand 50 μg/mL against methicillin-resistant Staphylococcus aureus(MRSA). Compounds 1and 2showed no cytotoxicity against the PANC1 human pancreatic carcinoma and NCI/ADR-RES ovarian adenocarcinoma cell lines at our standard test concentration of 5 μg/mL.

Bioactivity-guided fractionation of metabolites from the crinoid Holopus rangiiled to the discovery of two new phenanthroperylenequinone derivatives, gymnochromes E (1) and F (2). Gymnochrome E showed cytotoxic activity toward the NCI/ADR-Res with an IC50of 3.5 μM. It also inhibited histone deacetylase-1 with an IC50of 3.3 μM. Gymnochrome F was a moderate inhibitor of myeloid cell leukemia sequence 1 (MCL-1) binding to Bak. Two anthraquinone metabolites, emodic acid (4) and its new bromo derivative (5), were also isolated from the crinoid and show remarkable similarity to the phenanthroperylenequinone core, suggesting that these metabolites share the same polyketide biosynthetic pathway.

A new adenine-substituted bromotyrosine-derived metabolite designated as aphrocallistin (1) has been isolated from the deep-water Hexactinellida sponge Aphrocallistes beatrix. Its structure was elucidated on the basis of spectral data and confirmed through a convergent, modular total synthetic route that is amenable toward future analogue preparation. Aphrocallistin inhibits the growth of a panel of human tumor cell lines with IC50values ranging from 7.5 to >100 μM and has been shown to induce G1 cell cycle arrest in the PANC-1 pancreatic carcinoma cell line. Aphrocallistin has been fully characterized in the NCI cancer cell line panel and has undergone in vitroADME pharmacological profiling.