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1.
《Bioorganic & medicinal chemistry letters》2014,24(10):2329-2333
The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-factor Box–Behnken design (BBD). Regression analysis showed a good fit of the experimental data and the optimal condition was obtained as ethanol concentration, 74.5%; temperature 61.9 °C and extraction time, 13.5 h. The pancreatic lipase activity and extraction yield under optimal conditions were found to be 65.5% and 54.0%, respectively, which were well matched with the predicted value of 65.8% and 47.1%. Further fractionation of C. tricuspidata extract resulted in the isolation of compound 1, which was identified as 5,7,4′-trihydroxy-6,8-diprenylisoflavone. It inhibited pancreatic lipase activity with IC50 value of 65.0 μM. HPLC analysis suggested positive correlation between pancreatic lipase inhibition and 5,7,4′-trihydroxy-6,8-diprenylisoflavone of C. tricuspidata fruits. 相似文献
2.
《Bioorganic & medicinal chemistry》2020,28(11):115492
Effective chemotherapy for solid cancers is challenging due to a limitation in permeation that prevents anticancer drugs from reaching the center of the tumor, therefore unable to limit cancer cell growth. To circumvent this issue, we planned to apply the drugs directly at the center by first collapsing the outer structure. For this, we focused on cell–cell communication (CCC) between N-glycans and proteins at the tumor cell surface. Mature N-glycans establish CCC; however, CCC is hindered when numerous immature N-glycans are present at the cell surface. Inhibition of Golgi mannosidases (GMs) results in the transport of immature N-glycans to the cell surface. This can be employed to disrupt CCC. Here, we describe the molecular design and synthesis of an improved GM inhibitor with a non-sugar mimic scaffold that was screened from a compound library. The synthesized compounds were tested for enzyme inhibition ability and inhibition of spheroid formation using cell-based methods. Most of the compounds designed and synthesized exhibited GM inhibition at the cellular level. Of those, AR524 had higher inhibitory activity than a known GM inhibitor, kifunensine. Moreover, AR524 inhibited spheroid formation of human malignant cells at low concentration (10 µM), based on the disruption of CCC by GM inhibition. 相似文献
3.
The Proportion of Sediment-sensitive Invertebrates (PSI) index is a biomonitoring tool that is designed to identify the degree of sedimentation in rivers and streams. Despite having a sound biological basis, the tool has been shown to have only a moderate correlation with fine sediment, which although comparable to other pressure specific indices, limits confidence in its application. The aim of this study was to investigate if the performance of the PSI index could be enhanced through the use of empirical data to supplement the expert knowledge and literature which were used to determine the original four fine sediment sensitivity ratings. The empirical data used, comprised observations of invertebrate abundance and percentage fine sediment, collected across a wide range of reference condition temperate stream and river ecosystems (model training dataset n = 2252). Species were assigned sensitivity weights within a range based on their previously determined sensitivity rating. Using a range of weights acknowledges the breadth of ecological niches that invertebrates occupy and also their differing potential as indicators. The optimum species-specific sensitivity weights were identified using non-linear optimisation, as those that resulted in the highest Spearman's rank correlation coefficient between the Empirically-weighted PSI (E-PSI) scores and deposited fine sediment in the model training dataset. The correlation between percentage fine sediment and E-PSI scores in the test dataset (n = 252) was eight percentage points higher than the correlation between percentage fine sediment and the original PSI scores (E-PSI rs = −0.74, p < 0.01 compared to PSI rs = −0.66, p < 0.01). This study demonstrates the value of combining a sound biological basis with evidence from large empirical datasets, to test and enhance the performance of biomonitoring tools to increase confidence in their application. 相似文献
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《Bioorganic & medicinal chemistry》2020,28(9):115437
NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of 15N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae. 相似文献
7.
Human, rat and mouse pituitary tissues have been examined electron microscopically in transmission (TEM), scanning-transmission (STEM) and scanning (SEM) modes for the surface appearance of the secretory granules in tissue sections. Cryofixed and cryosectioned tissue showed only slightly protruding granule profiles which had a smooth surface. Cryofixed, freeze-dried and Epon embedded pituitaries, on the other hand, demonstrated swollen and furrowed surfaces over the granules after contact with water. This topography could also be seen after glutaraldehyde fixation but less after post-fixation in OsO4. The surface alterations in the sections of pituitary secretory granules are thought to be due to differences in the homogeneity of the resin infiltration, leaving resin-free openings where water can enter. It also seems probable that the Epon resin is more influenced by water than has been previously assumed, based on the findings of efficient elimination of osmium from the granules after incubation of tissue sections in water for only 10 min. 相似文献
8.
A comparison of direct and indirect methods for measuring leaf and surface areas of individual bushes 总被引:1,自引:0,他引:1
A. J. BRENNER M. CUETO ROMERO J. GARCIA HARO M. A. GILABERT L. D. INCOLL J. MARTINEZ FERNANDEZ E. PORTER F. I. PUGNAIRE M. T. YOUNIS 《Plant, cell & environment》1995,18(11):1332-1340
Indirect estimates of leaf area from measurements with three commercially available instruments (DEMON, LAI-2000 and Sunfleck Ceptometer) were compared with directly measured areas of individual Retama sphaerocarpa bushes. The three indirect methods gave good estimates of the total surface area of individual bushes. For the DEMON, the method of log-linear averaging of transmitted radiation gave estimates closer to directly measured surface area than the method of averaging transmission linearly. For the LAI-2000, estimated surface area index multiplied by canopy projected area gave the best agreement with directly measured values. For measurements with the Sunfleck Ceptometer, values of surface area estimated from the transmission of photosynthetic quantum flux density, without correcting for diffuse radiation, gave the best agreement with directly measured values. Surface areas estimated by the three instruments were not significantly different from directly measured total (leaf + branch + stem) surface areas. Leaf surface area could be calculated from estimated total surface area minus directly measured branch surface area. Measured branch surface area was linearly related to canopy projected area. 相似文献
9.
《Chirality》2017,29(7):340-347
Acrylamide (AM) was copolymerized with ethylene glycol dimethacrylate (EGDMA) in the presence of (R )‐1,1′‐binaphthalene‐2‐naphthol (BINOL) as the template molecules on the surface of silica gel by a free radical polymerization to produce a chiral stationary phase based on the surface molecularly imprinted polymer (SMIP‐CSP). The SMIP‐CSP showed a much better separation factor (α = 4.28) than the CSP based on the molecularly imprinted polymer (MIP‐CSP) without coating on the silica gel (α = 1.96) during the chiral separation of BINOL enantiomers by high‐performance liquid chromatography. The influence of the pretreatment temperature and the content of the template molecule ((R )‐BINOL) of the SMIP‐CSP, and the mobile phase composition on the separation of the racemic BINOL were systematically investigated. 相似文献
10.
《Journal of molecular recognition : JMR》2017,30(10)
An essential protein for bacterial growth, GTPase‐Obg (Obg), is known to play an unknown but crucial role in stress response as its expression increases in Mycobacterium under stress conditions. It is well reported that Obg interacts with anti‐sigma‐F factor Usfx; however, a detailed analysis and structural characterization of their physical interaction remain undone. In view of above‐mentioned points, this study was conceptualized for performing binding analysis and structural characterization of Obg‐Usfx interaction. The binding studies were performed by surface plasmon resonance, while in silico docking analysis was done to identify crucial residues responsible for Obg‐Usfx interaction. Surface plasmon resonance results clearly suggest that N‐terminal and G domains of Obg mainly contribute to Usfx binding. Also, binding constants display strong affinity that was further evident by intermolecular hydrogen bonds and hydrophobic interactions in the predicted complex. Strong interaction between Obg and Usfx supports the view that Obg plays an important role in stress response, essentially required for Mycobacterium survival. As concluded by various studies that Obg is crucial for Mycobacterium survival under stress, this structural information may help us in designing novel and potential inhibitors against resistant Mycobacterium strains. 相似文献