ABSTRACT
In previous work, a series of bioactive natural products had been isolated from the plant endophytic Streptomyces sp. CS, which was isolated from Maytenus hookeri. To mine new active metabolites, we describe introducing an alien carbamoyltransferase (asm21) gene into the strain CS by conjugal transfer. As a result, three recombinatorial mutants named CS/asm21-1, CS/asm21-2 and CS/asm21-4 were successfully constructed. Three mutants and wild type CS were cultured on solid medium, and the extracts were detected and analyzed by liquid chromatography-mass spectrometry (LC-MS). The LC-MS profiles showed several unknown peaks that were present in the spectra of extracts of the CS/asm21-4 cultured on oatmeal solid medium. Then, three new naphthomycins O-Q (1-3), a new macrolide hookerolide (4) as well as nine known compounds were obtained from the solid cultured medium. Their structures were identified by spectra data. These new compounds showed moderate antimicrobial activities.
Subject(s)
Macrolides/isolation & purification , Maytenus/microbiology , Streptomyces/chemistry , Carboxyl and Carbamoyl Transferases/genetics , Chromatography, Liquid , Conjugation, Genetic , Endophytes/chemistry , Mass Spectrometry , Microbial Sensitivity Tests , Microorganisms, Genetically-Modified , Molecular Structure , Plants, Medicinal/microbiology , Plasmids , Secondary MetabolismABSTRACT
The mushroom Stereum hirsutum is parasitized by Tremella aurantia to form a heterogeneous basidiocarp Jin'er, which has been used as food and folk medicine in Chinese society. In present work, the S. hirsutum was fermented in YMG broth, and four novel mixed terpenes, stereumamides A-D (1-4), which are sesquiterpenes combined with α-amino acids to form quaternary ammonium hybrids, were isolated from the Stereum hirsutum FP-91666 and their structures were elucidated by spectroscopic data analysis. Stereumamides A and D showed antibacterial activity against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium, with the minimum inhibitory concentration (MIC) values of 12.5-25.0⯵g/mL. The stereumamides A-D should be apparently the first example of naturally occurring a quaternary ammonium compound (QAC) conjugated by sesquiterpene with an α-amino acid. QAC is a common antibacterial agent in food industry, which is found in the mycelium of Stereum hirsutum would suggest that the complex basidiocarp is a functional food and veritable folk medicine.
Subject(s)
Agaricales/chemistry , Amino Acids/isolation & purification , Anti-Bacterial Agents/isolation & purification , Basidiomycota/chemistry , Quaternary Ammonium Compounds/isolation & purification , Sesquiterpenes/isolation & purification , Fermentation , Microbial Sensitivity Tests , Molecular Structure , Mycelium/chemistryABSTRACT
An endophytic fungus, Chaetomium sp. M453, was isolated from Huperzia serrata (Thunb. ex Murray) Trev. and subjected to phytochemical investigation. Three unusual C25 steroids, neocyclocitrinols E-G (1-3), and 3ß-hydroxy-5,9-epoxy-(22E,24R)-ergosta-7,22-dien-6-one (4) together with three known steroids were isolated from solid fermentation products of the fungus, which were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-ESI-MS experiments. The absolute configuration of 1 was determined by X-ray crystallographic analysis and CD analyses. The acetylcholinesterase inhibitory activities of compounds 1-4 were tested in vitro. Compound 4 showed weak acetylcholinesterase inhibitory activity.
Subject(s)
Chaetomium/chemistry , Cholinesterase Inhibitors/chemistry , Huperzia/microbiology , Steroids/chemistry , Cell Line, Tumor , Cholinesterase Inhibitors/isolation & purification , Humans , Molecular Structure , Plants, Medicinal/microbiology , Steroids/isolation & purificationABSTRACT
Studies of the EtOAc extract of the culture broth and methanol extract of the mycelium of Stereum insigne CGMCC5.57 led to the isolation of one new dihydrobenzofuran (1) and six known compounds (2-7). The structures of compounds were elucidated mainly by HRESIMS experiments, and 1D, 2D NMR spectroscopy analysis. This is the first report about the chemical constitutes of the fungus S. insigne.
Subject(s)
Basidiomycota/chemistry , Benzofurans/isolation & purification , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antinematodal Agents/chemistry , Antinematodal Agents/pharmacology , Bacillus subtilis/drug effects , Benzaldehydes/chemistry , Benzaldehydes/isolation & purification , Benzaldehydes/pharmacology , Benzofurans/chemistry , Drug Evaluation, Preclinical/methods , Ergosterol/analogs & derivatives , Ergosterol/chemistry , Ergosterol/isolation & purification , Ergosterol/pharmacology , Escherichia coli/drug effects , Magnetic Resonance Spectroscopy , Molecular Structure , Mycelium/chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
Biotransformation by the endophytes of certain plants changes various compounds, and this 'green' chemistry becomes increasingly important for finding new products with pharmacological activity. In this study, polyphyllin VII (PPL7) was biotransformed by endophytes from the medicinal plant Paris polyphylla Smith, var. yunnanensis. This produced a new compound, ZH-2, with pharmacological activity in vitro and in vivo. ZH-2 was more potent than PPL7 in selectively killing more chemoresistant than chemosensitive breast cancer cells. ZH-2 also re-sensitized chemoresistant breast cancer cells, as evidenced by the improved anti-cancer activity of commonly-used chemotherapeutic agent in vitro, in vivo, and in clinical samples. This anti-chemoresistance effect of ZH-2 was associated with inhibiting the epithelial-mesenchymal transition (EMT) pathway. Taken together, our findings are the first one to link biotransformation with a biomedicine. The results provide insights into developing new pharmacologically-active agents via biotransformation by endophytes.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Drug Discovery/methods , Drug Resistance, Neoplasm/drug effects , Saponins/metabolism , Saponins/pharmacology , Animals , Antineoplastic Agents/metabolism , Biotransformation , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Delftia acidovorans/metabolism , Dose-Response Relationship, Drug , Endophytes/metabolism , Epithelial-Mesenchymal Transition/drug effects , Female , Green Chemistry Technology , Humans , Liliaceae/microbiology , MCF-7 Cells , Mice, Nude , Tumor Burden/drug effects , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Three new naphthoquinones, astropaquinones A-C (1-3), were isolated from cultures of the freshwater fungus Astrosphaeriella papuana YMF 1.01181, together with the known compound, 6-hydroxy-2,4-dimethoxy-7-methylanthraquinone (4). The structures of the compounds were settled mainly by interpretation of their 1D and 2D NMR spectra. Astropaquinone B (2) and C (3) were found to possess a rare pyranonaphthoquinone skeleton containing a lactol ring. Furthermore, compounds 1-4 showed moderate antagonistic activity against nine fungi and four bacterial strains.
Subject(s)
Ascomycota/chemistry , Naphthoquinones/chemistry , Anthraquinones/chemistry , Anthraquinones/isolation & purification , Anthraquinones/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Microbial Sensitivity Tests , Naphthoquinones/isolation & purification , Naphthoquinones/pharmacology , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Three nematicidal cardenolides were obtained from the AcOEt extract of Nerium indicum Mill. by bioassay-guided fractionation. They include a new compound, 3beta-O-(beta-D-diginosyl)-14,15alpha-dihydroxy-5alpha-card-20(22)-enolide (1), and two known compounds, uzarigenin (2) and cardenolide N-1 (3). The median lethal concentrations (LC(50)) of compounds 1-3 against the nematodes Bursaphelenchus xylophilus, Panagrellus redivivus, and Caenorhabditis elegans at 72 h were 103.3, 49.0, and 45.4 mg l(-1), 257.0, 62.7, and 177.8 mg l(-1), and 242.9, 29.1, and 41.7 mg l(-1), respectively. This is the first report about the nematicidal activity of cardenolides.
Subject(s)
Antinematodal Agents/isolation & purification , Cardenolides/isolation & purification , Nerium/chemistry , Animals , Antinematodal Agents/pharmacology , Caenorhabditis elegans/drug effects , Cardenolides/pharmacology , Lethal Dose 50 , Nematoda/drug effects , Nuclear Magnetic Resonance, BiomolecularABSTRACT
OBJECTIVE: To investigate the effects of tetrandrine (Tet) on nuclear factor kappaB (NF-kappaB) expression in leukemia cell line K562 and multidrug-resistant K562/A02 cell line. METHODS: The activations of NF-kappaB in K562 and K562/A02 cells and the effects of 1 micromol/L Tet on NF-kappaB expression were determined by immunocytochemistry and Western blot assay. RESULTS: Tet had no effect on NF-kappaB expression in K562 cells after 6- and 12-hour treatment (P>0.05), and K562/A02 cells displayed higher level of NF-kappaB protein expression than their parental K562 cells (P<0.01). Tet could significantly down-regulate NF-kappaB protein expression and nuclear translocation in K562/A02 cells shown by immunocytochemistry and Western blot, and this decrease became more significant after 12-hour treatment than after at 6-hour treatment (P<0.05). CONCLUSION: Activation of NF-kappaB may be related to multidrug resistance of K562/A02 cell line. And the inhibition of NF-kappaB activation by Tet leads to multidrug resistance reversal in K562/A02 cell line.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzylisoquinolines/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , NF-kappa B/metabolism , Humans , K562 CellsABSTRACT
The root extract of Heracleum candicans Wall. exhibited antagonistic activities against nematodes Bursaphelenchus xylophilus (Steiner et Buhrer) Nickle and Panagrellus redivivus (Linn.) Goodey. Through bioassay-guided fractionations, three coumarins were obtained from the extract of H. candicans and determined to be 8-geranyloxypsoralen (1), imperatorin (2), and heraclenin (3) based on spectra data. All three compounds possessed nematicidal activities against the two tested nematodes. The median lethal concentrations (LC(50)) of compounds 1-3 at 72 h were 188.3, 161.7, and 114.7 mg L(-1) respectively against B. xylophilus and were 117.5, 179.0, and 148.7 mg L(-1) respectively against P. redivivus. This is the first report about species in the Umbelliferae family that possesses nematicidal activity.
Subject(s)
Antinematodal Agents/isolation & purification , Coumarins/isolation & purification , Heracleum/chemistry , Nematoda/drug effects , Animals , Antinematodal Agents/chemistry , Antinematodal Agents/pharmacology , Coumarins/chemistry , Coumarins/pharmacology , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistryABSTRACT
From the endophytic fungal strain Geotrichum sp. AL4, cultivated from the leaves of the neem tree (Azadirachta indica), four compounds, 1-4, were isolated from the AcOEt extract, including two new, chlorinated, epimeric 1,3-oxazinane derivatives. All compounds were assessed for their nematicidal activities against the nematodes Bursaphelenchus xylophilus and Panagrellus redivivus, and three out of the four isolates showed noticeable bioactivities.
Subject(s)
Antinematodal Agents/metabolism , Geotrichum/metabolism , Nematoda/drug effects , Animals , Antinematodal Agents/isolation & purification , Antinematodal Agents/pharmacology , Azadirachta , Fungi/metabolism , Geotrichum/physiology , Nematoda/growth & development , Plant Extracts/isolation & purification , Plant Extracts/metabolism , Plant Extracts/pharmacology , Plant LeavesABSTRACT
50 Traditional Chinese medicines (TCMs) were fermented by Bacillus subtilis and the antimicrobial activities of the fermented products were assayed against Mycobacterium tuberculosis and Penicillium avellaneum. The results showed that some products of them had stronger antimicrobial activities, but some weaker than the corresponding raw materials, still some had no change, which indicated that microorganism and TCM can effect each other during fermentation.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacillus subtilis , Drugs, Chinese Herbal/pharmacology , Mycobacterium tuberculosis/drug effects , Penicillium chrysogenum/drug effects , Plants, Medicinal/microbiology , Bacillus subtilis/metabolism , Drugs, Chinese Herbal/isolation & purification , Fermentation , Forsythia/chemistry , Forsythia/microbiology , Microbial Sensitivity Tests , Mycobacterium tuberculosis/growth & development , Penicillium chrysogenum/growth & development , Plants, Medicinal/chemistryABSTRACT
Poria cocos, a famous traditional Chinese medicine, was found to have nematicidal activity in experiments searching for nematicidal fungi. The experiment showed it could kill 94.9% of the saprophytic nematode, Panagrellus redivivue, 92.6% of the root-knot nematode, Meloidogyne arenaria, and 93.5% of the pine nematode, Bursaphelenchus xylophilus, on PDA plate within 12 hours. According to the nematicidal activity, three new compounds, 2, 4, 6-triacetylenic octane diacid, 2, 4, 5, 6-tetrahydroxyhexanoic acid and 3, 4-dihydroxy-2-keto-n-butyl 2,4,5,6-tetrahydroxyhexanate, were isolated from submerged cultures of Poria cocos. Of these, 2, 4, 6-triacetylenic octane diacid could kill 83.9% Meloidogyne arenaria and 73.4% Panagrellus redivivus at 500 ppm within 12 hours. Here, it is reported for the first time that Poria cocos has nematicidal activity.