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.

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

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.

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

OBJECTIVE: To investigate the effect of RITA on TP53 mutant human mantle cell lymphoma (MCL) cell line Mino and its possible mechanism. METHODS: Mino cells were cultured in RPMI-1640 and treated with RITA at a concentration of 0-16 μmol/L for 24,48,72 hours. Cell viability was assessed by CCK-8 assay. The cells were treated by RITA (0-8 μmol/L) for 48 h, the cell apoptosis induced by RITA was detected by annexin V/PI flow cytometry. Western blot was performed to evaluate the expression of protein BCL-2, Caspase-3, Cleaved Caspase-3, PARP, MDM2, and P53 in Mino cells. RESULTS: After treatment with 0.5, 1, 2, 4, 8, and 16 μmol/L RITA for 48 h, the proliferation inhibition rate of Mino cells was (1.2±5.6)%, (14.9±4.9)%, (41.7±5.0)%, (61.8±2.4)%, (70.2±2.8)%, and (70.8±2.4)%, respectively. RITA could inhibit the proliferation of Mino cells significantly, and statistical analysis showed that the inhibition rate was increased with the increasing of RITA concentration (r=0.767). After the cells were treated by 4 μmol/L RITA for 24, 48, and 72 h, the proliferation inhibition rate was (25.2±3.8)%, (61.8±2.4)%, and (87.0±0.7)%, respectively. Satistical analysis showed that the inhibition rate was also increased with the increasing of treatment time (r=0.978). The apoptosis rate of Mino cells treated by 0, 2, 4, and 8 μmol/L RITA for 48 h was (5.4±0.4)%, (15.3±0.6)%, (38.7±1.7)%, and (50.8±1.1)%, respectively, and it showed dose-dependent manner (r=0.961). Western blot showed that with the increasing of RITA concentration, the BCL-2 protein expression was decreased in a dose-dependent manner (r=0.932), moreover, PARP cleavage and Caspase-3 activation were found, while the protein expression of MDM2 and P53 showed no change. CONCLUSION RITA can inhibit the proliferation and induce the apoptosis of Mino cells significantly. The mechanism may be dependent on the Caspase pathway, but independent on the P53 pathway.
Apoptosis ; Cell Line, Tumor ; Cell Survival ; Furans ; Humans ; Lymphoma, Mantle-Cell ; Mutation ; Tumor Suppressor Protein p53

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

This study was to build a canine portal hypertension model by intra-portal administration of high polymer material polyurethane and organic solvent tetrahydrofuran mixed solutions in order to evaluate the effectiveness of the model. Twelve local crossbreed dogs were selected randomly, with intra-portal administration of 8% (weight/volume) polyurethane- tetrahydrofuran solutions through an incision in the upper abdomen to build the portal hypertension model. We measured the portal vein pressure before modeling, during modeling, and four-, eight-, and twelve- weeks after modeling, respectively. Then we evaluated the effectiveness of the model comparing values of data with those data obtained before modeling started, which were regarded as the normal values. The results showed that the portal vein pressure rose by 2. 5 times after the solution administrated instantly as much as that before modeling, and maintained at 1. 5 times after 4 weeks. This method presents an easy operation, low animal mortality and reliable model of portal hypertension. Its less abdominal adhesions and its ability in keeping normal anatomic structure specially make it suit for surgical research of portal hypertension.
Animals ; Disease Models, Animal ; Dogs ; Furans ; adverse effects ; Hypertension, Portal ; Polyurethanes ; adverse effects ; Portal Vein ; physiopathology