Synthesis of Laminarin Oligosaccharide Derivatives Having d‐Arabinofuranosyl Side‐Chains

An efficient glycosylation strategy was applied in the synthesis of β‐d‐glucopyranosyl‐(1→3)‐[α‐d‐arabinopyranosyl‐(1→4)]‐β‐d‐glucopyranosyl‐(1→3)‐β‐d‐glucopyranosyl‐(1→3)‐[α‐d‐arabinopyranosyl‐(1→6)]‐d‐glucopyranose to secure β‐d‐(1→3) glycosidic bond formation between glucopyranosyl residues. The new strategy using a 4,6‐O‐benzylidenated acceptor avoided generation of the α major isomer in the attempted β‐d‐(1→3) glycosylation under standard glycosylation conditions. The hexasaccharide we prepared showed about 30% tumor growth inhibition towards S180 model study.     

Synthesis and in vitro antitumor activity of novel diaryl urea derivatives

A series of novel diaryl ureas containing 4-[（2-amino-6-trifluromethyl）pyrimidine-4-yl]piperazine-l-yl group were synthesized and evaluated for their cytotoxic activities in a panel of human cancer cell lines. Compared with the reference drug Sorafenib,some compounds showed more potent and a broader spectrum of anti-cancer activities.Among them,compound 2p demonstrated significant inhibitory activities against MDA-MB-231,HT-29 and MCF-7 cell lines with IC₅₀ values of 0.016,0.63,0.001μmol/L, respectively.     

Synthesis and Antitumor Evaluation of Some Newly Synthesized Pyrazolopyrimidine and Pyrazolotriazolopyrimidine Derivatives

A series of novel pyrazolo[3,4-d]pyrimidine 2b, 3, 5b, pyrazolotetrazolopyrimidine 4, and pyrazolotriazolopyrimidine derivatives 6a,b–10a,b have been synthesized and characterized by elemental analysis and spectroscopic data. Furthermore, the cytotoxicity and in vivo antitumor evaluation of some prepared compounds have been assessed, and derivatives 1a and 6b revealed promising activity in comparison to that of Cisplatin.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Fabrication of fucoxanthin/2-hydroxypropyl-β-cyclodextrin inclusion complex assisted by ultrasound procedure to enhance aqueous solubility,stability and antitumor effect of fucoxanthin

Fucoxanthin (Fx) possesses multiple bioactivities such as antitumor, antioxidant and anti-inflammatory activities, but its application is limited due to the poor water solubility, low bioavailability, and instability to some external harsh conditions. In this study, a stable inclusion complex of Fx and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) was prepared with the aid of ultrasound, which was characterized by scanning electron microscope, Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry techniques. The phase solubility analysis and absorption spectroscopy results showed that Fx formed stoichiometry 1:2 inclusion complex with 2-HP-β-CD, and this could be well proved by molecular simulation. Structural analyses and molecular docking study indicated that Fx was successfully encapsulated into the cavity of 2-HP-β-CD, promoting it soluble in water and stable against heat, storage and gastrointestinal environments. In addition, Fx/2-HP-β-CD inclusion complex exhibited excellent antitumor activity against HCT116 and Caco-2 cell lines with IC₅₀ values of 12.0 μΜ and 14.86 μΜ, respectively. Therefore, it could be a potentially promising way to promote the application of Fx in pharmaceuticals and functional foods by HP-β-CD encapsulation strategy.     

Surface Coordination Polymerization of Ethylene by Hydrozirconation‐Immobilized Metallocene

Hydrozirconation on vinyl‐terminated substrates (silicon wafer and nanosilica sphere) is employed as an efficient way for immobilization of zirconocene catalyst through Zr C bonds, which is applied in surface coordination ethylene polymerization producing surface‐tethered polyethylene (PE). The formation of Zr C σ bond induced by hydrozirconation provides an initiator precursor for growing a layer of PE covalently linked onto substrates. The results from SEM, AFM, and TEM show that the surface polymerization is controlled by hydrozirconation. Surface pattern or core–shell structure with crystalline PE coating can be formed, when silicon wafer is selectively functionalized with vinyl‐groups or vinyl‐modified nanosilica is applied. It is believed that hydrozirconation for the synthesis of zirconocene initiator can be a versatile route to prepare polyolefin hybrid materials.

     

吡啶联异噁唑类化合物的设计、合成及抗肿瘤活性

根据已知的激酶变构抑制剂与其靶点激酶的X射线共晶结构,设计了一系列以吡啶联异噁唑为中心结构的潜在激酶变构抑制剂.以2-甲基-5-硝基-3-吡啶甲酸甲酯为原料,通过形成酰胺、磺酰胺和连接嘧啶片段等衍生化手段合成了21个新的吡啶联异噁唑类化合物,其结构经1H NMR,13C NMR和MS确证.采用噻唑蓝(MTT)法测试了所合成化合物的体外抗肿瘤活性,初步测试结果表明该类化合物对肿瘤细胞的增长具有显著的抑制作用.     

Ethylene polymerization by rigid benzene ring centered dinuclear metallocene (Ti, Zr)/MAO systems

Two rigid benzene centered dinuclear metallocene complexes C₆H₂[(CH₂C₅H₄)₂MCl₂]₂, M = Ti (1), Zr (2) have been prepared by treating two equivalents of TiCl₄ and ZrCl₄ with the tetralithium salt of the ligand C₆H₂(CH₂C₅H₅)₄-1,2,4,5 in toluene and characterized by ¹H NMR and elemental analysis. Both complexes are effective catalysts for ethylene polymerization in the presence of methylaluminoxane (MAO). The influence of [MAO]/[Cat] molar ratio, catalyst concentration, polymerization temperature and time has been tested in detail. The catalytic activity of complex 2 is more than two times higher than that of complex 1, which is still more active than that of the tetranuclear titanocene C₆H₂[CH₂C₅H₄Ti(C₅H₅)Cl₂]₄-1,2,4,5 (5). On the other hand, the catalytic activities of 1 and 2 is slightly lower than that of the dinuclear metallocene complexes C₆H₄[CH₂C₅H₄Ti(C₅H₄CH₃)Cl₂]₂-1,3 (3) and C₆H₄[CH₂C₅H₄Zr(C₅H₅)Cl₂]₂-1,3 (4), respectively, which is related to the limited intermolecular rotation of the metallocene units in 1 and 2. The melting points above 130 °C indicate a polyethylene formed by complexes 1 and 2 with highly linear and highly crystalline. GPC spectra show that polyethylene produced by complexes 1 and 2 has a broad and even bimodal molecular weight distribution (MWD).     

Synthesis and cytotoxic activity of resveratrol-based compounds

In continuation of our studies on compounds with a resveratrol-based scaffold two compounds with N-containing functional groups have been synthesized and screened for their inhibitory effect on the growth of the human cancer cell lines HT29, 518A2, AsPC-1, BxPC-3, and PC-3. Compound 4, but not 1, demonstrated pronounced in vitro cytotoxicity against all these cancer cell lines, thus making this compound a promising candidate for further preclinical in vivo studies. Correspondence: Thomas Erker, Department of Medicinal Chemistry, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.     

Virus-Like Particle-Induced cGAS-STING Activation and AIM2 Inflammasome-Mediated Pyroptosis for Robust Cancer Immunotherapy

cGAS-STING-mediated DNA sensing is demonstrated to be critical for launching antitumor immunity. However, DNA-based cGAS-STING agonists are rarely reported owing to low cell permeability, poor biostability and, especially, limited length of exogenous DNA. Here, we present a virus-like particle which is self-assembled from long DNA building blocks generated through rolling-circle amplification (RCA) and covered with cationic liposomes. Based on long and densely packed DNA structure, it could efficiently induce liquid phase condensation of cGAS and activate STING signaling to produce inflammatory cytokines. Moreover, this virus-like particle could also trigger the formation of AIM2 inflammasome to induce gasdermin D-mediated pyroptosis, boosting antitumor immunity. Thus, this study provides a simple and robust strategy for cancer immunotherapy for clinical application. This is the first study to report the intrinsic immunogenicity of RCA products, thus facilitating their biomedical applications.