In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.
Cell Line ; Cell Proliferation ; Fermentation ; Furans ; Lipids ; Maleic Anhydrides ; MCF-7 Cells ; Structure-Activity Relationship

Some degradation products from lignocellulose pretreatment strongly inhibit the activities of cellulolytic enzymes and ethanol fermentation strains, thus the efficient removal of the inhibitor substances ("detoxification") is the inevitable step for the biotransformation processes. In this study, the biological detoxification of furfural by a newly isolated fungus, Amorphotheca resinae ZN1, was studied and the metabolic pathways of furfural degradation was analyzed. The metabolic pathway of furfural degradation in A. resinae ZN1 was described as follows: first, furfural was quickly converted into the low toxic furfuryl alcohol; then the furfuryl alcohol was gradually converted into furfural again but under the low concentration under aerobic condition, which was not lethal to the growth of the fungi; furfural continued to be oxidized to furoic acid by A. resinae ZN1. It is likely that furoic acid was further degraded in the TCA cycle to complete the biological degradation of furfural. The present study provided the important experimental basis for speeding up the biodetoxification of furfural by A. resinae ZN1 and the rate-limiting step in the lignocellulose biotransformation to ethanol.
Biodegradation, Environmental ; Biotransformation ; Ethanol ; metabolism ; Fermentation ; Fungi ; metabolism ; Furaldehyde ; isolation & purification ; metabolism ; Furans ; metabolism ; Lignin ; metabolism

Lignocellulose is the most abundant renewable organic carbon resource on earth. However, due to its complex structure, it must undergo a series of pretreatment processes before it can be efficiently utilized by microorganisms. The pretreatment process inevitably generates typical inhibitors such as furan aldehydes that seriously hinder the growth of microorganisms and the subsequent fermentation process. It is an important research field for bio-refining to recognize and clarify the furan aldehydes metabolic pathway of microorganisms and further develop microbial strains with strong tolerance and transformation ability towards these inhibitors. This article reviews the sources of furan aldehyde inhibitors, the inhibition mechanism of furan aldehydes on microorganisms, the furan aldehydes degradation pathways in microorganisms, and particularly focuses on the research progress of using biotechnological strategies to degrade furan aldehyde inhibitors. The main technical methods include traditional adaptive evolution engineering and metabolic engineering, and the emerging microbial co-cultivation systems as well as functional materials assisted microorganisms to remove furan aldehydes.
Aldehydes ; Fermentation ; Furans ; Lignin/metabolism*

OBJECTIVETo study the influence of the quorum sensing inhibitor brominated furanone on Porphyromonas gingivalis (P. gingivalis) biofilm formation.

METHODSDoubling dilution method was used to determine the minimal inhibition concentration (MIC) of brominated furanone on P. gingivalis. Absolute ethyl alcohol added in P. gingivalis bacterial suspension was used as the negative control, while P. gingivalis bacterial suspension as blank control. The influences of 1/4MIC, 1/2MIC, MIC, 2MIC of brominated furanone on P. gingivalis biofilm formation were studied by the optical density determination and scanning electron microscope (SEM).

RESULTSFour groups of brominated furanone with different concentrations were shown to inhibit P. gingivalis biofilm formation. With the increased concentration of brominated furanone, optical density of P. gingivalis suspension decreased. The biofilm structures of 1/4MIC group, 1/2MIC group and MIC group were loose. Only scattered P. gingivalis cells but no biofilm structure was seen in 2MIC group.

CONCLUSIONBrominated furanone could inhibit P. gingivalis biofilm formation without the influence on bacterial growth. The future application of this chemical compound may provide a new possibility for the antimicrobial treatment of periodontal disease.

OBJECTIVETo develop an HPLC method for determination of clemastanin B which has anti-viral activity in Radix Isatidis and compare the contents of clemastanin B in the drugs from different origins.

METHODThe samples were separated on an ZORBAX SB-C18 (4.6 mm x 250 mm, 5 microm) column with the mobile phase of acetonitrile-water (11:89). Flow rate was 1.0 mL x min(-1). The detection wavelength was set at 225 nm. Column temperature was 30 degrees C.

RESULTThe linear range of clemastanin B was 0.0615-1.8441 microg (r = 0.9995), the average recovery was 97.74%, RSD was 1.4% (n=9). The contents of clemastanin B were in the range of 0.269-0.900 mg x g(-1) in Radix Isatidis from different origins.

CONCLUSIONThe method for quantitation of clemastanin B in Radix Isatidis was accurate and reliable, which can be used to evaluate the quality of Radix Isatidis.

Crassostrea sikamea (C.sikamea) is an important edible and medicinal seafood in China. In the present study, a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea (EAECs) for the first time. In addition, the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium (MTS) assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro. Moreover, flazin (20 μg·mL
Animals ; Carbolines ; Crassostrea ; Furans ; Lymphocytes ; Rats ; Rats, Sprague-Dawley ; Spleen

Eribulin is a synthetic microtubule dynamics inhibitor that was developed from a marine natural product halichondrin B. It exhibited in vitro and in vivo activities against a wide number of malignancies. A number of advanced phase trials showed improved survival following eribulin treatment in pretreated advanced breast cancer patients. This review provides an overview of the background to the therapeutic use of eribulin in oncology, including its pharmacology, pharmacokinetics, clinical efficacy, safety, and potential economic factors.
Breast ; Breast Neoplasms ; Drug Evaluation ; Ethers, Cyclic ; Furans ; Humans ; Ketones ; Macrolides ; Microtubules

To study the chemical constituents from the leaves of Celastrus gemmatus Loes., chromatographic methods were used to isolate and purify the chemical constituents, their structures were elucidated by the physiochemical characteristics and spectral data. Nine compounds were obtained and identified as (-)-massoniresinol 3a-O-beta-D-glucopyranoside (1), ambrosidine (2), isolariciresinol 9-O-beta-D-glucopyranoside (3), kaempferol 3-O-beta-D-glucopyranoside (astragalin) (4), kaempferol 3-O-rutinoside (5), kaempferol 3-O-neohesperidoside (6), apigenin 7-O-beta-D-glucuronide (7), apigenin 7-O-beta-D-glucuronide methyl ester (8) and D-sorbitol (9). Compound 1 is a new compound, the others are isolated from this genus for the first time, and this is the first time to report lignan compounds from genus Celastrus.
Celastrus ; chemistry ; Furans ; chemistry ; isolation & purification ; Lignans ; chemistry ; isolation & purification ; Plant Leaves ; chemistry

OBJECTIVEHeadspace solid-phase microextraction (HS-SPME) was used pre-concentration procedure for the determination of tetrahydrofuran in urine by gas chromatography with hydrogen flame detector.

METHODSSeveral parameters controlling SPME was studied and optimised: SPME fiber, extraction time and extraction temperature, desorption time and desorption temperature.

RESULTSUnder optimal conditions, the correlation coefficient was 0.9998 and good recoveries (range from 93.0% ∼ 100.8%) were achieved, the detection limit was 0.5 µg/L.

CONCLUSIONThe method can be applied to the determination of trace amount of tetrahydrofuran in urine.

Carnosine (beta-Ala-L-His) has high antioxidant activity, and it is widely used in biology, chemical engineering, medicine and other fields. Its analogue syntheised in non-aqueous solvent and catalyzed by enzymes is high-effective but low-price, so it has great prospect. Here, we synthesized a carnosine analogue imidazole 4(5)-alanylamide-5(4)-carboxylic acid with imidazole-4,5-dicarboxylic acid and L-Alanine as substrates, alpha-chymotrypsin as catalyst in tetrahydrofuran (THF) solvent. Based on the orthogonal experiments, the optimized synthetic conditions are 4,5-dicarboxylic acid: L-alanine = 1:3 (m/m), alpha-chymotrypsin: substrates (4,5-dicarboxyl acid and L-alanine) = 1:200 (m/m), pH 8 phosphate buffer:THF = 1.6:10 (V/V), reaction temperature 35 degrees C, time 1.5 h. We separated the product with silica gel G60 thin-layer chromatography (TLC), and a new spot appeared at Rf (ratio to front) = 0.81; then the new spot was purified and characterized with UV spectra, high performance liquid chromatogram (HPLC) and 13C NMR (13C nuclear magnetic resonance). The UV spectra shows a new absorption peak at 310 nm, and the peak in 253 nm is largely strengthened; HPLC reserve times are all 4.5 min at 253 nm, 310 nm, 330 nm; 13C NMR shows 8 carbons. Combing with the catalytic mechanism of alpha-chymotrypsin, structure of the analogue is confirmed, i.e., imidazole 4(5)-alanylamide-5(4)-carboxylic acid.
Carnosine ; analogs & derivatives ; biosynthesis ; chemistry ; Catalysis ; Chromatography, High Pressure Liquid ; Chymotrypsin ; metabolism ; Furans ; chemistry ; Solvents