Metal complexes of anthranilic acid derivatives: A new class of noncompetitive α-glucosidase inhibitors

Metal complexes of anthranilic acid derivatives that constitute a novel class of non-sugar-type aglucosidase inhibitors were synthesized and assessed in vitro for inhibitory activity. All of the Ag(I)complexes(9–16) inhibited a-glucosidase at the nanomolar scale, while 3,5-dichloroanthranilic acid silver(I)(9) was the most potent(IC_(50)= 3.21 nmol/L). Analysis of the kinetics of enzyme inhibition indicated that the mechanism of the newly prepared silver complexes was noncompetitive. The structure-activity relationships were also analyzed, and they are discussed in this report.     

Schiff碱Cu(Ⅱ)配合物的合成,表征,及其抑制脲酶活性的机理研究

为了得到一种新型脲酶抑制剂,以5-氯水杨醛和2-氨甲基哌啶合成Schiff碱配体,再与硝酸铜反应合成了一种Schiff碱Cu(Ⅱ)配合物。分别采用元素分析,单晶衍射、红外光谱测试技术对其进行表征,采用热重分析法探讨其对热稳定性,采用酚红法测定该配合物抑制脲酶活性的大小,采用Lineweaver-Burk模型研究其抑制脲酶的动力学机理,通过分子对接技术探讨配合物与脲酶的作用方式,并对其抑制机理进行分析。结果表明,目标配合物属于单斜晶系,P2₁/n空间群,四方形结构,它通过氢键、疏水键与脲酶形成稳定的结合模式;抑制脲酶活性的机制属于竞争性和非竞争性混合型抑制机制,其竞争性抑制作用大于非竞争性抑制作用。配合物对刀豆脲酶的IC₅₀为10.03μmol·L^-1,远低于常规脲酶抑制剂(45.06μmol·L^-1),从理论上解释了体外抑制脲酶活性的实验结果。     

基于水杨醛席夫碱锌配合物交联稳定化荧光聚合物胶束的合成及其对铜离子的荧光响应性

以S-十二烷基-S'-(α,α'-二甲基-α″-乙酸)-三硫代碳酸酯(DMAT)为链转移剂、2-羟基-5-乙烯基苯甲醛(HVB)为单体,利用可逆加成-断裂链转移自由基聚合法(RAFT)合成结构明确、数均相对分子质量可控的水杨醛聚合物(PHVB)。将PHVB直接地与单端胺基功能化聚乙二醇(m PEG-NH2)按n(—NH2group)/n(—CHO group)=0.50投料进行醛-胺缩合反应,获得接枝率为50%的两亲性接枝水杨醛席夫碱聚合物PHVB-graft-PEG。采用凝胶渗透色谱仪(GPC)和核磁共振氢谱(1H NMR)对合成的聚合物的数均相对分子质量和结构进行了确证。将PHVB-graft-PEG直接地分散于无水乙醇中,自组装形成以聚乙烯水杨醛席夫碱为核、聚乙二醇为壳的胶束,然后以所得胶束为微反应器,与Zn(OAc)2进行配位反应得到外壳为可溶性链段PEG,内核为发光水杨醛席夫碱锌配合物的PHVB-graft-PEG/Zn~(2+)交联稳定化胶束。通过紫外-可见分光光谱(UV-Vis)、荧光发射光谱(FLL)、动态光散射(DLS)和透射电子显微镜(TEM)分别对胶束的交联稳定化过程进行了表征。研究结果表明,经交联稳定化后,PHVB-graft-PEG/Zn~(2+)胶束在干燥后仍可在水和常见有机溶剂中再分散形成粒径大小约为100 nm、在约460 nm处发射出蓝光荧光的纳米粒子,并且可作为荧光传感器,在水溶液中对Cu~(2+)离子进行选择性识别,其荧光淬灭率与Cu~(2+)离子浓度(0~50μmol/L范围内)呈线性关系,最低检测下限至0.5μmol/L,而其它共存离子如Cd~(2+)、Mg~(2+)、Ni~(2+)、Pb~(2+)、Ca~(2+)、Hg~(2+)、Al3+、Mn~(2+)等对Cu~(2+)离子的荧光响应性没有干扰,即可实现对Cu~(2+)离子进行定量检测。     

娃儿藤碱类似物DCB-3501的全合成及其细胞毒性

以3,4-二甲氧基苯甲醛与3,4-二甲氧基苯乙酸为起始原料,经Perkin缩合、自由基氧化偶联反应、Swern氧化、还原胺化及付克酰基化等7步反应全合成了娃儿藤碱类似物DCB-3501,其结构经¹H NMR和ESI-MS确证。体外细胞毒性测试结果表明：DCB-3501对人结肠癌细胞HCT116、人胃癌细胞BGC-823、人肝癌细胞HepG-2、人宫颈癌细胞HeLa和人大细胞肺癌细胞H460的IC₅₀分别为20.0 μmol·L^-1, 50.9 μmol·L^-1, 2.1 μmol·L^-1, 65.8 μmol·L^-1和30.8 μmol·L^-1。     

Synthesis and structure-activity relationships study of α-aminophosphonate derivatives containing a quinoline moiety

Two series of a-aminophosphonate derivatives containing a quinoline moiety have been designed and synthesized by introducing bioactive quinoline scaffold to a-aminophosphonate. The in vitro cytotoxic activities of target compounds were first investigated against two human cancer cell lines including Eca109 and Huh7 by MTT assay. Results revealed that most of target compounds exhibited moderate to high antitumor activities against the tested cancer cell lines and some demonstrated more potent inhibitory activities compared with Sunitinib. Among them, compounds 4b2 and 4b4 containing methylsubstituted aniline group were found to be more active than Sunitinib against both of two cancer cell lines, with IC50 in the range of 2.26 mmol/L–7.46 mmol/L.     

Expeditious synthesis,antileishmanial and antioxidant activities of novel 3-substituted-4-hydroxycoumarin derivatives

A series of novel 3-substituted-4-hydroxycoumarin derivatives 6(a–1) were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. These compounds were evaluated for antileishmanial activity against Leishmania donovani promastigotes and antioxidant activity(DPPH-radical scavenging activity). Two compounds, 6h(IC_(50)= 9.90 μmol/L) and 6i(IC_(50)= 6.90 μmol/L) displayed potent antileishmanial activity when compared with standard antileishmanial agents pentamidine(IC_(50)= 16.15 μmol/L) and miltefosine(IC_(50)= 12.50 μmol/L). Three compounds, 6c(IC_(50)= 10.79 μmol/L), 6h(IC50= 10.60 μmol/L), and 6i(IC_(50)= 10.73 μmol/L) showed significant antioxidant activity favorably with the antioxidant standards butylated hydroxy toluene(IC_(50)= 16.47 μmol/L) and ascorbic acid(IC_(50)= 12.69 μmol/L). A molecular docking study of compounds 6(a–1) suggested a possible mode of binding with the Adenine phosphoribosyltransferase enzyme of L.donovani. ADME properties were predicted in silico and support the potential of 6(a–1) to show favorable drug-like properties.     

Development of bis-thiobarbiturates as successful urease inhibitors and their molecular modeling studies

Bis-thiobarbiturate derivatives 1–15 have been synthesized, characterized by1 HNMR and EI-MS and screened for urease inhibition. All compounds showed various degree of urease inhibitory activity with IC_(50) values ranging 7.45 0.12 74.24 0.81 mmol/L while the standard thiourea behaved normally(IC_(50) = 21.10 0.12). Compounds 1(IC_(50) = 7.45 0.12 μmol/L), 9(IC_(50) = 18.17 1.03 μmol/L) and 13(IC_(50) = 8.61 0.45 μmol/L) showed excellent urease inhibitory activity in the series. Molecular modeling studies were performed to understand the binding site with the bimetallic nickel center of the enzyme.Structure-activity relationship has also been established for these compounds. This study identified bisthiobarbiturate as a novel class of urease inhibitors.     

Tuning plasmon absorption of unmodified silver nanoplates for sensitive and selective detection of copper ions by introduction of ascorbate

Silver nanoplates as novel optical sensors for Cu^2＋ detection have been demonstrated.Silver nanoplates are synthesized via previous H_2O_2-NaBH_4 cyclic oxidation-reduction reactions.With introduction of ascorbate as mild reductants,Cu^2＋ ions are reduced into Cu~＋ and the Cu^＋ is further reduced to Cu,which is deposited on the surface of the silver nanoplates.The deposition of the Cu on the surface of the silver nanoplates allows a significant red-shift of their plasmon absorption.Therefore,trace Cu^2＋ can be detected.The shift of the plasmon absorption wavelength of silver nanoplates is proportional to the Cu^2＋concentration over a range of 40-340 μmol L~（-1） with a limit of detection of 9.0 μmol L~（-1）.Moreover,such silver nanoplate-based optical sensors provide good selectivity for Cu^2＋ detection,and most other metal ions do not disturb its detection.Moreover,the practicality of the proposed sensor was tested.This Cu^2＋assay is advantageous in its simplicity,selectivity,and cost-effectiveness.     

Synthesis of novel β-propanamides to inhibit cholesteryl ester transfer protein(CETP)

A novel series of β-propanamide derivatives as inhibitors of cholesteryl ester transfer protein(CETP)were synthesized.Previously,H3(IC_(50) 2 μmol/L) was observed to inhibit CETP moderately(Xie et ah,2016).Structural modifications based on H3 led to discovery of the successful CETP inhibitor,known as 1-methyl-4-arylpyrazole.Using a similar approach,compound Q08 was identified as a highly potent CETP inhibitor with an IC_(50) of 490 nmol/L in vitro.     

花粉多肽对钙调素的拮抗作用研究

研究了在Ca²⁺存在下荞麦花粉肽及其类似物和丹磺酰标记的钙调素(D-CaM)的相互作用,结果表明,除肽BP-1外,都能与D-CaM结合而形成复合物。利用荧光光谱法测定了这些复合物的解离常数K_d.在所研究的多肽中以BP-13拮抗CaM作用最强,其K_d值为4.6×10^-2μmol/L,抑制钙依赖性磷酸二酯酶活性的IC₅₀为2.2μmol/L.我们还发现,当D-丙氨酸残基取代没有亲和性的BP-1中甘氨酸残基时,其亲和性明显提高。     

Graphene oxide–MnO_2 nanocomposite-modified glassy carbon electrode as an efficient sensor for H_2O_2

In this study, a new facile preparation method of nanocomposites consisting of graphene oxide and manganese dioxide nanowires(GO/MnO_2 NW_s) was developed. The morphology, structure and composition of the resulted products were characterized by transmission electron microscopy, X-ray diffraction and N_2 adsorption and desorption. The GO/MnO_2 nanocomposite was used as an electrode material for non-enzymatic determination of hydrogen peroxide. The proposed sensor exhibits excellent electrocatalytic performance for the determination of hydrogen peroxide in phosphate buffer solution(PBS, pH7) at an applied potential of 0.75 V. The non-enzymatic biosensor for determination of hydrogen peroxide displayed a wide linear range of 4.90 mmol L~(-1)–4.50 mmol L~(-1)with a correlation coefficient of 0.9992, a low detection limit of 0.48 mmol L~(-1) and a high sensitivity of 191.22μA(mmol L~(-1))~(-1)cm~(-2)(signal/noise, S/N = 3). Moreover, the non-enzymatic biosensor shows an excellent selectivity.     

新型含游离羟基鱼藤素衍生物的合成及其抗肿瘤活性

以鱼藤酮为原料经3步反应合成鱼藤素; 鱼藤素分别经三溴化硼脱甲基和硼氢化钠还原合成了4个新型含游离羟基的鱼藤素衍生物（3a~3c和4）,其结构经^1H NMR,¹³C NMR和LC-MS表征。初步的抗肿瘤活性测定结果表明,12-羟基鱼藤素（4）对人乳腺癌细胞MCF-7和人肺癌细胞H299的抑制活性较好,其IC₅₀分别为0.11 μmol·L^-1和0.01 μmol·L^-1,优于阳性对照药Deguelin。     

Synthesis and α-glucosidase inhibitory activity of chrysin,diosmetin, apigenin,and luteolin derivatives

Several derivatives have been synthesized from chrysin, diosmetin, apigenin, and luteolin, which were isolated from diverse natural plants. The α-glucosidase inhibitory activity of these compounds was evaluated. The glucosidase inhibitory activity of all derivatives （IC50 〈 24.396 μmol]L） was higher compared with that of the reference drug, acarbose （IC50=563.601 ±40.492μmol/L）, and 1- deoxynojirimycin （IC50 = 226.912± 12.573 μmol/L）. O3＇,O7-Hexyl diosmetin （IC50 = 2.406 ± 0.101μmol/L） was the most potent inhibitor identified. These compounds showed a higher inhibitory ability compared with their precursors except the luteolin derivatives. In general, the inhibitory activity of the synthetic derivatives was enhanced with long alkyl chains at positions 3＇, 4＇ and 7 of the flavonoid.     

Thermochemical studies on copper(II) and nickel(II) complexes of the Schiff base derived from 2-(2-aminophenyl)benzimidazole and salicylaldehyde

Microcalorimetric measurements were made on copper(II) and nickel(II) complexes of the Schiff base (L) derived from 2-(2-aminophenyl)benzimidazole and salicylaldehyde. The complexes were of the general type MX₂L₂ with M = Cu or Ni, and X = Cl, Br, NO₃ or ClO₄. The enthalpies of decomposition of the solid complexes to solid products, MX₂ and L, were derived. Despite showing some variation depending on the anion, the average binding enthalpy of the ligand to nickel was 47.5 ± 7.3 kJ mol⁻¹, greater than that to copper, 16.8 ± 3.5 kJ mol⁻¹ by 30.7 ± 8.1 kJ mol⁻¹.     

One-step co-electrodeposition of graphene oxide doped poly(hydroxymethylated-3,4-ethylenedioxythiophene) film and its electrochemical studies of indole-3-acetic acid

A novel graphene oxide(GO) doped poly(hydroxymethylated-3,4-ethylenedioxythiophene)(PEDOTM)film has been achieved via one-step co-electrodeposition and utilized for electrochemical studies of indole-3-acetic acid(IAA).The incorporation of GO into PEDOTM film facilitated the electrocatalytic activity and exhibited a favorable interaction between the PEDOTM/GO film and the phytohormone during the oxidation of IAA.Under optimized conditions,differential pulse voltammetry and square wave voltammetry were used for the quantitative analysis of IAA,respectively,each exhibiting a wide linearity range from 0.6 μmol L~(-1) to 10 μmol L~(-1) and 0.05 μmol L~(-1) to 40 μmol L~(-1),good sensitivity with a low detection limit of 0.087 μmol L~(-1) and 0.033 μmol L~(-1) respectively,as well as good stability.With the notable advantages of a green,sensitive method,expeditious response and facile operation,the as-prepared PEDOTM/GO organic-inorganic composite film provides a promising platform for electrochemical studies of IAA.     

N-(2-吡啶甲基)-L-丝氨酸铜配合物的合成、晶体结构及抑制蛋白酪氨酸磷酸酶活性

在甲醇溶液中, 还原希夫碱HL[N-(2-吡啶甲基)-L-丝氨酸]与CuCl₂·2H₂O以摩尔比1∶1反应, 得到1个新的中性单核铜配合物[CuLCl(H₂O)](Ⅰ). 通过X射线单晶衍射、 元素分析、 红外光谱、 电喷雾质谱和粉末X射线衍射分析等对其进行了表征. 晶体结构分析表明, 在该配合物中还原希夫碱以三齿双螯合环配位到中心铜离子, 同时氯离子和溶剂水分子也参与配位, 形成1个具有四方锥构型的五配位铜(Ⅱ)配合物, 该配合物通过分子间弱相互作用连接成二维超分子结构. 生物活性测试结果表明, 配合物Ⅰ能有效抑制蛋白酪氨酸磷酸酶1B(PTP1B)和T细胞蛋白酪氨酸磷酸酶(TCPTP), IC₅₀值分别为0.32和0.45 μmol/L.     

Design,Synthesis and Activities of Aziridine Derivatives of N5-Methyltetrahydrofolate Against Methionine Synthase

Aziridine derivatives of N⁵-methyltetrahydrofolate were designed and synthesized based on the mechanism of methionine synthase, and their biological activities were investigated as well. The aziridine derivatives 1 and 6 exhibited superior inhibitory activities(IC₅₀: 5.05 and 4.15 μmol/L, respectively) compared to the corresponding chain analogue 4(IC₅₀=24.42 μmol/L). The results suggest that the aziridine derivatives can get potential activities against nucleophilic methionine synthase.     

Phenolic constituents from the roots of Alangium chinense

Three new phenolics(1–3) and twenty-eight known compounds(4–31) were isolated from an ethanolic extract of roots of Alangium chinense. Compound 11 exhibited antiviral activity against Coxsackie virus B3 with IC50 values of 16.89 mmol/L. Compounds 1, 10–17, 19–21, and 23 showed strong antioxidant activity against Fe~(2+)-cysteine-induced rat liver microsomal lipid peroxidation, with IC_(50) values of 0.14–8.18 mmol/L.     

Isolation and Stucture Elucidation of Diterpenes from Wedelia prostrata and Their Cytotoxicity Activities

In this paper, a new diterpene together with seven known diterpenes was isolated from Wedelia prostrata. The chemical structure of the new compound was elucidated via 1D and 2D nuclear magnetic resonance(NMR) techniques and mass spectrometry and identified to be 3α-phenylpropionoyloxy-ent-kaur-16-en-oic acid(1). The isolated diterpenes were tested for their cytotoxicity activities via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. The results show that compounds 1, 2, 3, 4 and 6 exhibit different levels of cytotoxic activities. Especially, compound 2 shows significant cytotoxicity toward HeLa and A549 cell lines(IC₅₀=6.14 and 8.76 μmol/L).     

New cyclopiane diterpenes with anti-inflammatory activity from the sea sediment-derived fungus Penicillium sp. TJ403-2

Three new rare cyclopiane diterpenes(1-3),together with thirteen known compounds(4-16),were isolated and identified from a sea sediment-derived fungus Penicillium sp.TJ403-2.The planar and relative structures of compounds 1-3 were elucidated by HRESIMS,one-and two-dimensional NMR analyses,and their absolute configurations were further established by X-ray crystallography experiment.Compounds 1-3 were evaluated for the anti-inflammatory activity against LPS-induced NO production,and compound 1 showed notable inhibitory potency with an IC50 value of2.19±0.25μmol/L,which was three fold lower than the positive control indomethacin(IC50=8.76±0.92μmol/L).Further Western blot and immunofluorescence experiments demonstrated its mechanism of action to be that 1 inhibited the NF-κB-activated pathway,highlighting it as a promising starting point for the development of new anti-inflammatory agents.