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Graphical abstract Highlights • Two new compounds were isolated from Anemarrhena asphodeloides in Vietnam. • 1H and 13C NMR data of Anemarrhenoside A and Timosaponin C-IV were supported. • Timosaponin C-IV showed cytotoxicity against both A549 and Hela cell lines. Abstract Two new steroidal glycosides 1 and 2 have been isolated from the n -butanol extract portion of Anemarrhena asphodeloides Bunge (A.asphodeloides), a widely used plant as Traditional Chinese Medicine. Their structures have been confirmed through a variety of analytic approaches including 1D and 2D-NMR spectroscopic techniques as well as mass spectrometry data. Moreover, cytotoxic activity evaluation demonstrated that compound 2 exhibited micromole level cytotoxic effects against A549 and Hela cancer cells. [ABSTRACT FROM AUTHOR]

A series of AKBA derivatives were synthesized, and evaluated as potent VEGFR-2 inhibitors. The initial biological evaluation indicated that the introduction of C-24 amide group or a heterocycle at C-2,3 position effectively improved the potency. Further structure–activity relationship analysis showed that amide ( 7 , 23 , 25 , and 26 ) and heterocycle ( 19 , 34 , and 36 ) substituted AKBA derivatives displayed more potential anti-proliferation activities than AKBA ( 1 ) on HUVECs that express high levels of VEGFR-2. Among all tested compounds, compounds 7 and 19 exhibited the best potency (IC 50 : 2.36 and 2.13 μM) and obvious inhibitory activities with VEGFR-2 inhibition rates of 96% and 94% at 50 μM, respectively. [ABSTRACT FROM AUTHOR]

Abstract: A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure–activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. [Copyright &y& Elsevier]

The structure and particle distribution of the abrasive used in chemical mechanical polishing (CMP) directly affect the performance of polishing and quality of the resulting surface. The ceria (CeO 2) nanomaterial has been extensively employed in polishing abrasives. Increasing the Ce3+ content is known to improve removal efficiency and enable optimal surface quality. In this study, we increased the Ce3+ content on the CeO 2 surface by growing CeO 2 nanoparticles in situ on graphene oxide (GO; CeO 2 @GO) to develop novel composite abrasives for the high-performance CMP of silicon wafers. The designed composite abrasive fully utilized the special structure of GO and the effect on the charge-transfer between CeO 2 and GO, which increase the Ce3+ content and number of chemical reaction sites available during the polishing process. This accelerates the generation rate of the oxide layer on the surface of the silicon wafer and increases the removal rate while improving surface quality. The removal rate of the composite abrasives reached 190.58 ± 13 nm/min, which is 50% higher than that of pure CeO 2 abrasives. Moreover, the average surface roughness (Ra) of 0.278 ± 0.07 nm within the confines of a 5.0 × 5.0 μm2 region was achieved using the novel composite abrasives. This study offers a straightforward method to enhance the content of Ce3+ in materials and provides a novel route for obtaining efficient composite abrasives. [ABSTRACT FROM AUTHOR]

Abstract: A one-pot procedure was developed for the synthesis of isoindolin-1-imine derivatives by a simple three-component condensation of 2-cyanobenzaldhyde, ammonium acetate, and 4-hyroxycoumarin derivatives or 1,3-dicarbonyl compounds or 4-hydroxyquinolin-2(1H)-one in ethanol under reflux for 20–60 min with excellent yields. The advantages of this procedure are operational simplicity, excellent yields, and short reactive time, without catalyst, easy workup, and green environmental impact. [Copyright &y& Elsevier]

Histone deacetylase 6 (HDAC6) is a zinc-dependent HDAC that mainly modulates the acetylation status of non-histone substrates, such as α-tubulin and heat shock protein 90 (HSP90). The activity of HDAC6 plays a critical role in cell proliferation, protein trafficking and degradation, cell shape, migration, as well as regulation of immunomodulatory factors. For this reason, HDAC6 influences the progress of cancers, neurodegenerative disorders, and autoimmune responses. In the last few years, the discovery of selective HDAC6 inhibitors (HDAC6is) has become an attractive research area as five HDAC6is are being investigated in phase I/II clinical trials. However, the hydroxamic acid functional group still represents the predominant zinc-binding group (ZBG), that often suffers from poor pharmacokinetics and mutagenic potential, thus impairing the application of hydroxamate-based HDAC6is for long-term therapies. On the other hand, mercaptoacetamide (MCA)-based HDAC6is comprise a class of compounds that, in some cases, display nanomolar HDAC6 potency and a thousand-fold selectivity over class I HDAC isozymes. Moreover, MCA-based HDAC6is lack the mutagenicity associated with the hydroxamate function and display pharmacological effects, demonstrating the potential of this particular ZBG to improve upon the drug-like properties of HDAC6is. Herein, we summarize for the first time the structure-activity relationships (SARs) of MCA-based HDAC6is, discuss their HDAC6 selectivity at the molecular level using inhibitor-HDAC co-crystal structures, and further provide our perspective regarding their drug metabolism, pharmacokinetics, and pharmacological properties. Image 1 • Thiol-derived HDAC inhibitors avoid the mutagenic potential of hydroxamates. • Mercaptoacetamide-based analogs show excellent HDAC6 potency and selectivity. • The unique thiolate-zinc coordination is responsible for the HDAC6 selectivity. • Brain penetrable mercaptoacetamide shows efficacy in Alzheimer's disease models. [ABSTRACT FROM AUTHOR]

A new series of fluorinated 5-HT 2C agonists were designed and synthesized on the basis of our previous work on 2-phenylcyclopropylmethylamines as a potential approach for the treatment of central nervous system disorders. Key fluorinated cyclopropane moieties were constructed through transition metal catalyzed [2 + 1]-cycloaddition of aromatic vinyl fluorides, and the absolute stereochemistry of the representative compound (–)- 21a was established. Functional activity measuring calcium flux at 5-HT 2 receptors reveals high potency for compounds (+)- 21a-d. In particular, (+)- 21b had no detectable 5-HT 2B agonism and displayed reasonable selectivity against 5-HT 2A. Molecular docking studies were further performed to explain the compounds' possible binding poses to the 5-HT 2C receptor. Image 1 • New fluorinated cyclopropylmethylamine derivatives as 5-HT 2C agonists. • Fluorinated cyclopropane moiety was constructed through [2 + 1]-cycloaddition. • Compound (+)- 21b had high potency at 5-HT 2C (EC 50 = 8 nM) without 5-HT 2B agonism. • Molecular modelling to predict possible binding poses to 5-HT 2C receptor. [ABSTRACT FROM AUTHOR]

A novel series of N -aryl- N ′-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the EGFR L858R/T790M. The most representative compound 28 showed high activity against EGFR L858R/T790M kinase (IC 50  = 4 nM) and 22-fold selectivity against wild type EGFR. Moreover, compound 28 potently inhibited EGFR L858R/T790M phosphorylation (IC 50  = 41 nM) and cellular proliferation (IC 50  = 37 nM) in the H1975 cell line, while being significantly less toxic to A431 cells. Further, compound 28 exhibited a great selectivity in a mini-panel of kinases. [ABSTRACT FROM AUTHOR]

In this work, we provide a paradigm how to realize white light emission by utilizing the energy transfer from the Bi3+ to Eu3+ ions. First, a novel Bi3+ activated phosphor set of highly oxygen-deficient perovskite derivatives (Ba 3 YGa 2 O 7.5 , BYGO) were synthesized through the conventional high-temperature solid-state method. The crystal structure was confirmed by Rietveld refinement. Then, Eu3+ was introduced to the phosphor composition to construct energy transfer pathway with Bi3+. The emission color of the BYGO:Bi3+,Eu3+ phosphors can be changed from cyan to white and orange-red by altering the Bi3+/Eu3+ doping ratio. The energy transfer from the Bi3+ to Eu3+ ions was ascribed to dipole-dipole interaction. Finally, a single-component WLED device with a color-rendering index of 84.9 was successfully prepared by employing a near-ultraviolet chip and the BYGO:Bi3+,Eu3+ phosphors. This work not only indicates that the as-prepared BYGO:Bi3+,Eu3+ phosphors are a potential candidate for near-ultraviolet WLED, but also demonstrated that energy transfer is an avenue for single-phased white light emission. [Display omitted] • The cyan phosphor Ba 3 YGa 2 O 7.5 :Bi3+ was synthesized for the first time. • The energy transfer from the Bi3+ to Eu3+ ions is constructed. • Adjusting the doping ratio of Bi3+ to Eu3+ realizes multicolor emission. • A single-phased WLED with a color rendering index of 84.9 was achieved. [ABSTRACT FROM AUTHOR]

Abstract: Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy in the treatment of cancers. Identification of natural compounds capable of circumventing MDR with minimal adverse side effects is an attractive goal. Here, we found that H6, a gypenoside aglycon from Gynostemma pentaphyllum, displayed potent anti-MDR activity. Average resistant fold (RF) of H6 is 1.03 and 1.04 in KB/VCR and MCF-7/ADR cells compared to their parental cells. H6 alone ranging from 2μmol/l to 40μmol/l (μM) did not display a significant anti-proliferative effect on KB/VCR cells and other cells, while the compound at these concentrations enhanced the cytotoxicity of vincristine (VCR) to KB/VCR cells. H6 showed a significant synergistic effect in combination with VCR. By quantification of sub-G1 fraction cells, H6 also enhanced the VCR-induced apoptosis in a dose-dependent manner. The short time treatment with H6 increased the intracellular accumulation of rhodamine 123 (Rho123) and 5(6)-carboxyfluorescein diacetate (CFDA) in KB/VCR cells. Further studies showed that H6 treatment resulted in the decrease of the RNA transcript level of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP). H6 inhibited the function of P-gp by stimulating P-gp ATPase activity and decreased MRP1 expression with a blockade of STAT3 phosphorylation. These findings suggest that H6, a multi-targets reversal agent with no significant toxic effect, may be a potential candidate to circumvent the P-gp and MRP1-mediated MDR. [Copyright &y& Elsevier]