Two novel spiroaminals, marineosins A and B (1, 2), containing two pyrrole functionalities, were isolated from cultures of a marine sediment-derived actinomycete related to the genus Streptomyces. The marineosins, which appear to be derived from unknown modifications of prodigiosin-like pigment pathways, showed significant inhibition of human colon carcinoma in an in vitro assay (IC 50 = 0.5 μM for marineosin A) and selective activities in diverse cancer cell types.Marine actinomycetes have become an important source of structurally unique secondary metabolites 1 including many with potent biological acitvities. Among the actinomycetes frequently recovered from marine samples are members assignable to the genus Streptomyces, a diverse group of soil bacteria that account for the majority of microbially derived antibiotics discovered as of 2002. 2 Although the genus Streptomyces is best known from terrestrial soils, phylogenetically-related groups have been reported from marine samples including some that require seawater for growth 3 suggesting a high level of marine adaptation.Here, we report the isolation, structure determination, and biological activity of two unique spiroaminals, marineosins A and B (1, 2), from a marine-derived Streptomyces-related actinomycete (our strain CNQ-617).Marineosin A (1) 4 analyzed for the molecular formula C 25 H 35 N 3 O 2 ([M] + m/z 409.2726) by EI high-resolution mass spectrometry. The LRESIMS also showed ions that analyzed for [M +H] + at m/z 410. This molecular formula, which contained ten degrees of unsaturation, was further indicated by analysis of 1 H and 13 C NMR spectral data (Table 1). Initial interpretation of DEPT and 13 C NMR spectal data showed that the majority of the proton signals were from methylene protons. The 1 H NMR spectrum of 1, measured in acetone-d 6 , also contained five aromatic protons at δ 5.44 (d, J = 3 Hz), 5.68 (d, J = 3 Hz), 6.11 (dd, J = 2.5, 3.5 Hz), 6.37 (dd, J = 1.5, 3.5 Hz), and 6.97 (dd, J = 1.5, 2.5 Hz). NMR analysis using both COSY and HMBC methods (Figure 1) showed correlations which illustrated that these proton signals were components of two pyrrole rings.wfenical@ucsd.edu. COSY NMR correlations between H-11 (δ 5.68) and H-12 (δ 5.44), and HMBC correlations from H-11 to C-10, C-12 and C-13, H-12 to C-10, C-11 and C-13, suggested the presence of a 2, 5-disubstituted pyrrole ring. The proton coupling constants of H-11 and H-12 (d, J = 3 Hz) also supported this substitution pattern. The remaining three aromatic proton signals showed COSY correlations that allowed the connectivity of C-1/C-2/C-3 to be established. Observed HMBC correlations from H-1 to C-3 and C-4, H-2 to C-4, and H-3 to C-1 and C-4 indicated that these olefinic protons could be assigned to a pyrrole ring with mono-substitution at C-4. Additional evidence, which confirmed the presence of this pyrrole ring, were the expected carbon and proton chemical shifts and proton coupling constants that matched with other known pyrrole derivatives. NIH Public Access NIH-PA ...

During the course of our ongoing work to discover new inhibitors of biofilm formation of Staphylococcus aureus from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete Hypoxylon fragiforme for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison. Out of 21 cytochalasans, 13 showed significant inhibition of Staphylococcus aureus biofilm formation at subtoxic levels. These findings indicate the potential of cytochalasans as biofilm inhibitors for the first time, also because the minimum inhibitory concentrations (MIC) are independent of the anti-biofilm activities. However, cytochalasans are known to be inhibitors of actin, making some of them very toxic for eukaryotic cells. Since the chemical structures of the tested compounds were rather diverse, the inclusion of additional derivatives, as well as the evaluation of their selectivity against mammalian cells vs. the bacterium, will be necessary as next step in order to develop structure-activity relationships and identify the optimal candidates for development of an anti-biofilm agent.

Two new steroidal sulfates, eurysterols A (1) and B (2), were isolated from an undescribed marine sponge of the genus Euryspongia collected in Palau. The structures of the new compounds were assigned by NMR spectroscopic data interpretation. Compounds 1 and 2 showed cytotoxicity against human colon carcinoma (HCT-116) cells with IC50 values of 2.9 and 14.3 microg/mL, respectively, and exhibited antifungal activity against amphotericin B-resistant and wild-type strains of Candida albicans with MIC values, in turn, of 15.6 and 62.5 microg/mL.