Retinestatin, a Polyol Polyketide from a Termite Nest-Derived Streptomyces sp.

A new polyol polyketide, named retinestatin (1), was obtained and characterized from the culture of a Streptomyces strain, which was isolated from a subterranean nest of the termite Reticulitermes speratus kyushuensis Morimoto. The planar structure of 1 was elucidated on the basis of the cumulative analysis of ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance spectroscopic data. The absolute configuration of 1 at 12 chiral centers was successfully assigned by employing a J-based configuration analysis in combination with ROESY correlations, a quantum mechanics-based computational approach to calculate NMR chemical shifts, and a 3 min flash esterification by Mosher's reagents followed by NMR analysis. Biological evaluation of retinestatin (1) using an in vitro model of Parkinson's disease revealed that 1 protected SH-SY5Y dopaminergic cells from MPP+-induced cytotoxicity, indicating its neuroprotective effects.

QM-HiFSA-Aided Structure Determination of Succinilenes A-D, New Triene Polyols from a Marine-Derived Streptomyces sp.

Based on profiles of secondary metabolites produced by marine bacteria obtained using LC/MS, succinilenes A-D (1-4), new triene polyols, were discovered from a culture of a Streptomyces strain SAK1, which was collected in the southern area of Jeju Island, Republic of Korea. The gross structures of 1-4 were primarily determined through analysis of NMR spectra. The double bond geometries of the succinilenes, which could not be established from conventional ¹H NMR spectra because of the highly overlapped olefinic signals, were successfully deciphered using the recently developed quantum-mechanics-driven ¹H iterative full spin analysis (QM-HiFSA). Succinilenes A-C (1-3) displayed inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production, indicating their anti-inflammatory significance. These three compounds (1-3) commonly bear a succinic acid moiety, although succinilene D (4), which did not inhibit NO production, does not have this moiety in its structure. The absolute configurations of succinilenes A-D (1-4) were established through J-based configuration analysis, the modified Mosher's method following methanolysis, and CD spectral analysis.

Separacenes A-D, novel polyene polyols from the marine actinomycete, Streptomyces sp.

Separacenes A-D (1-4), novel polyene polyols, were isolated from Streptomyces sp. collected from the southern area of Jeju Island, Korea. The chemical structures of 1-4 were established by NMR, mass, UV, and IR spectroscopy as well as the modified Mosher's method. Separacenes A-B (1-2), which share an identical planar structure but possess different relative configurations, bear tetraene units flanked by two diol moieties, whereas the stereoisomeric separacenes C-D (3-4) possess a triene moiety between two diol substructures. Separacenes A-D each contain a terminal olefinic methylene. Separacene A displayed inhibitory activity against Candida albicans isocitrate lyase and weak cytotoxicity against both the colon carcinoma cell line HCT-116 and the lung cancer cell line A549.

Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis.

Background: Streptococcus mutans, an important Gram-positive pathogen in dental caries, uses sortase A (SrtA) to anchor surface proteins to the bacterial cell wall, thereby promoting biofilm formation and attachment to the tooth surface. Design: Based on activity-guided separation, inhibitors of S. mutans SrtA were isolated from Juniperus chinensis and identified through combined spectroscopic analysis. Further effects of isolated SrtA inhibitor on S. mutans were evaluated on bacterial aggregation, adherence and biofilm formation. Results: Six compounds (1-6) were isolated from the dried heartwood of J. chinensis. A novel compound designated 3',3"-dihydroxy-(-)-matairesinol (1) was identified, which exhibited potent inhibitory activity toward S. mutans SrtA (IC50 = 16.1 µM) without affecting microbial viability (minimum inhibitory concentration > 300 µM). The results of subsequent bioassays using compound 1 indicated that this compound inhibits S. mutans aggregation, adhesion and biofilm formation on solid surfaces by inhibiting SrtA activity. The onset and magnitude of inhibition of adherence and biofilm formation in S. mutans treated with compound 1 at 4× the SrtA IC50 are comparable to the behaviors of the untreated srtA-deletion mutant. Conclusion: Our findings suggest that small-molecule inhibitors of S. mutans SrtA may be useful for the prevention of dental plaque and treatment of dental microbial diseases.

Dragocins A-D, Structurally Intriguing Cytotoxic Metabolites from a Panamanian Marine Cyanobacterium.

Dragocins A-D (1-4) were isolated from a dark-red wooly textured marine cyanobacterium collected in Boca del Drago, Panama. Dragocins A-C (1-3) possessed 2,3-dihydroxypyrrolidine, 1-hydroxy-5- O-Me-benzoyl, and 4'-substituted-ß-ribofuranose moieties that connected to form a nine-membered macrocyclic ring. Dragocins A-C are members of a unique hybrid structural class with substitution at the C-4' position of a ribofuranose unit. Of the four new compounds, dragocin A was the most potent cytotoxin to human H-460 lung cancer cells.