Xiao-Long Cui

Naphthospironone A: An Unprecedented and Highly Functionalized Polycyclic Metabolite from an Alkaline Mine Waste Extremophile

Extremophiles, microorganisms surviving in various extreme environments, have developed unique defenses that either tolerate or favor extremes of pH, temperature, salinity, pressure and radiation. These special characteristics frequently lead to synthesis of novel molecules encompassing a variety of unusual structural classes with significant biological activities. In comparison with extremophiles from natural environments, microorganisms isolated from man-made extreme environments are emerging as a valuable resource for bioactive natural products. For example, Stierle and coworkers have recently isolated several novel molecules, including berkelic acid, which inhibits protein-cleaving enzymes caspase-1 and matrix metalloproteinase-3, from acidophilic fungi found in Berkeley Pit Lake (an abandoned copper mine filled with acidic water at pH 2.7). This implies that there are miniature natural product libraries to be found in the most unexpected places. Extremophiles surviving in man-made extreme environments around the world could be an untapped mine for drug discovery. Inspired by Stierle s work, we profiled the metabolite patterns of alkalophilic actinomycetes, which were isolated from an alkaline soil sample (pH 10) collected from the Datun tin mine tailings area (Yunnan province, Southwest China; 103818’36’ E, 23822’12’ N; formed by the materials remaining after extraction and beneficiation of tin ores over 50 years). The TLC and HPLC-DAD analysis of the acetone extract of Nocardiopsis sp. (YIM DT266) revealed the presence of a new metabolite, naphthospironone A (1, Scheme 1). The compound was obtained as a colorless solid (3 mgL ) by standard chromatographic procedures from solid fermentation (30 L) of the strain. Even though some structural elements resemble those of actinomycetes metabolites, such as a-naphthocyclinone (2) and b-naphthocycli-

Griseusin D, a New Pyranonaphthoquinone Derivative from a Alkaphilic Nocardiopsis sp

A new pyranonaphthoquinone antibiotic, griseusin D (1) was isolated from the cultural fluid of the alkaphilic Nocardiopsis sp. The structure was determined as 5′-one-4-hydroxy-12-methoxygriseusin by spectroscopic methods, comparison with reported data and single-crystal X-ray analysis. 1 displayed strong cytotoxicity against human leukemia cells (HL60) and modest cytotoxicity against human lung adenocarcinoma cell lines (AGZY) with IC50 values of 0.23 and 19.6 μg/ml, respectively. It also exhibited weak antifungal activity against Alternaria alternate with MIC of 140 μg/ml.

Griseusins F and G, spiro-naphthoquinones from a tin mine tailings-derived alkalophilic Nocardiopsis species.

Griseusins F (1) and G (2), two 2a-hydro-8a-(2-oxopropyl)-substituted spiro-naphthoquinones with a previously undescribed C23 polyketide skeleton, were isolated from a Yunnan tin mine tailings-derived alkalophilic actinomycete, Nocardiopsis sp. YIM DT266. Their complete structure assignments with the absolute stereochemistry were elucidated by spectroscopic data, X-ray crystal diffraction, calculation of optical rotation, and CD spectroscopic analysis. Compounds 1 and 2 exhibited strong cytotoxicity (IC50 0.37-0.82 μM) and antibacterial activity (MIC 0.80-1.65 μg/mL) against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) in vitro.

1H and 13C NMR assignments of eight nitrogen containing compounds from Nocardia alba sp.nov (YIM 30243T)

An unprecedented new natural product named nocarsin A (1), 5H‐4a,6,7a‐triazacyclopenta[cd]indene‐5,7(6H)‐dione (1), together with seven known compounds lumichrome (2), cyclo (L‐Leu‐L‐Tyr) (3), cyclo (L‐Ala‐L‐Ile) (4), cyclo (L‐Ala‐L‐Leu) (5), cyclo (L‐Val‐L‐Ala) (6), 5‐methyluracil (7) and uracil (8), was isolated from Nocardia alba sp.nov (YIM 30243T), which was isolated from a soil sample collected from Yunnan Province, P. R. China. NMR techniques including COSY, HSQC, ROESY, and HMBC were used to elucidate the structures of these compounds. We report the unambiguous assignments of the 1H and 13C NMR spectra of the new compound nocarsin A (1). Copyright

Oligomycins A and C, major secondary metabolites isolated from the newly isolated strain Streptomyces diastaticus

During the screening program for fungicides, one actinomycete strain ECO 00047 was isolated with the potential activity against fungus. According to the morphology and analysis of the nucleotide sequence of the 16S rRNA gene (1500 bp) this isolate was identified as Streptomyces diastaticus. The active compounds were separated by silica gel column chromatography, Sephadex LH-20 gel filtration and then purified by flash chromatography on C18 (20–45 μm). The chemical structure of the bioactive compounds I and II were elucidated, based on the spectroscopic data of MS, IR, UV, 1H-NMR, 13C-NMR and X-ray single crystal diffraction analysis. Compounds I and II were identical with oligomycins A and C, the macrolide antibiotics which have been known to be produced by Streptomyces diastatochromogenes, S. libani and S. avermitilis. The two compounds exhibited a strong activity against Aspergillus niger, Alternaria alternata, Botrytis cinerea and Phytophthora capsici but no activity toward bacteria. Although the two above antibiotics were known, their isolation has so far not been reported from S. diastaticus.

Phenazinolins A-E: novel diphenazines from a tin mine tailings-derived Streptomyces species

Phenazinolins A-E (1-5), which possess a carbon skeleton unique to diphenazines (the azabicyclo[3.3.1]nonadienol moiety in 1-3 and the oxabicyclo[3.3.1]nonadienol moiety in 4 and 5), were isolated from tin mine tailings-derived Streptomyces diastaticus YIM DT26, with 1-3 exhibited appreciable cytotoxicity and antibiotic effects.

A new isoflavone derivative from Streptomyces sp. YIM GS3536

A new natural product named 7-O-methyl-8-chlorogenistein (1) was isolated together with eight known isoflavones, 8-chlorogenistein (2), kakkatin (3), 7-O-methyl genistein (4), genistein (5), daidzein (6), glycitin (7), genistin (8), and daidzin (9), from the metabolites of Streptomyces strain YIM GS3536, which was isolated from soil sample collected from Yunnan Province, China. We report the unambiguous assignments of the 1H and 13C NMR spectra of the new compound 7-O-methyl-8-chlorogenistein (1). Compound 1 exhibited appreciable cytotoxicity against human melanoma cell lines (B16) and human leukemia cell lines (HL60) with IC50 values of 17.5 and 19.2 μM, respectively. The MIC values of 1 for Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Candida albicans were in the range of 23–35 μM.

Cytotoxic metabolites of Streptimonospora salina

Streptimonospora salina gen. nov., sp. nov. was found to produce three phenoxazinone antibiotics, 2-amino-3H-phenoxazin-3-one (1), 2-methylamino-3H-phenoxazin-3-one (2), 2-acetylamino-3H-phenoxazin-3-one (3), and one phenazine antibiotic, phenazine-1-carboxylic acid (4). The chemical structures of the compounds were determined using 1D and 2D NMR spectrometry and electrospray mass spectrometry (ESMS). Compounds 1-4 exhibited modest cytotoxicity against a human renal carcinoma cell line ACHN with IC50 values of 35.4, 12.4, 65.4, and 82.9 μM, respectively. Compound 2 was discovered for the first time from a biological origin.