水溶性高支化多糖及硫酸酯衍生物抗癌活性研究

从虎奶菇菌核中提取出一种水溶性高支化葡聚糖,并用氯磺酸和吡啶在无水二甲亚砜中进行硫酸酯衍生化,制备出硫酸酯衍生物.用巴比赛小鼠动物实验研究该多糖及其硫酸酯衍生物的体内抗肉瘤S-180活性,以及用肝癌细胞株HepG2研究体外活性,同时讨论多糖分子尺寸与抗癌活性的关系.通过形态学、组织切片、以及酶联免疫法研究硫酸酯化对多糖抗肿瘤活性的影响.结果表明,支链多糖的均方根旋转半径在42.5~113 nm之间,显示出较高的体内和体外抗肿瘤活性,硫酸酯衍生物的均方根旋转半径在17.8~34.9 nm之间,抗癌活性随其分子尺寸的增大而逐渐提高.多糖及其硫酸酯衍生物能诱导人体肝癌HepG2细胞凋亡,且具有时间依赖性.它们对免疫反应的调节作用可通过肿瘤坏死因子TNF-α来介导.     

五内酯E和长南酸的分离与结构

从浙江临安产的长梗南五味子(Kadsura longipedunculata Finet. etGagnep.)根皮中分得2个新三萜化合物: 五内酯E(Schisanlactone E, 1)和长南酸(changnanic acid 2)以及3个已知物: 五内酯B(schisanlactone B,3)、meso-二氢愈创木脂酸(meso-dihydoguaiaretic acid,4)和β-谷甾醇(β-sitosterol,5)。1和2在体外对白血病p-388细胞有明显地抑制作用, IC50分别为1μg/mL和10μg/mL。本文报道其分离、鉴定与结构研究。     

Study of fungal degradation products of polycyclic aromatic hydrocarbons using gas chromatography with ion trap mass spectrometry detection

Representatives of polycyclic aromatic hydrocarbons (PAHs) were degraded by ligninolytic fungus Irpex lacteus. The products were analyzed by GC-Ion trap mass spectrometry. The combination of full scan mass spectra, product ion scans (MS-MS) and derivatization of the degradation products of anthracene, phenanthrene, fluoranthene and pyrene provided further insight in the degradation mechanism initiated by I. lacteus. Particularly, the product ion scans enabled the interpretation of unknown degradation products, even though they were only produced at trace level. Most of the structures suggested were later confirmed with authentic standards.     

Synthesis,characterization, and antitumour studies of some curcuminoid analogues and their aluminum complexes

Aluminum(III) complexes of three curcuminoid analogues [1,7-diphenyl-1,6-heptadiene-3,5-dione, HL¹; 1,7-bis(2-hydroxyphenyl)-1,6-heptadiene-3,5-dione, HL²; and 1,7-bis(4-ethoxyphenyl)-1,6-heptadiene-3,5-dione, HL³] of [AlL₃] stoichiometry were synthesized and characterized by UV, IR, ¹H NMR, and mass spectral data. The compounds were investigated for cytotoxic and antitumor activities. The aluminum chelates are remarkably active compared to free curcuminoid analogues. The aluminum complex of HL² with hydroxyl in the phenyl ring was most active towards Ehrlich ascites carcinoma cells (concentration needed for 50% inhibition of 5?μg/mL) and cultured L929 cells (1?μg/mL produced 60?+?3% cell death). Increase in lifespan and reduction of solid tumor volume in mice were also largest for the aluminum complex of HL². The study reveals that the antitumor activities of curcuminoids are more enhanced by complexation with aluminum than with transition metal ions.     

Synthesis and Antitumor Activity of a New 7-Azaindole Derivative

We designed and synthesized a 7-azaindole derivative（TH1082）, which was characterized by 1^H NMR and 13^C-NMR. We investigated its antitumor effects on human melanoma A375 cells, human liver cancer SMMC cells and human breast cancer MCF-7 cells in vitro via 3-（4,5-dimethyldiazol-2-yl）-2,5-diphenyl-tetrazolium bromide （MTT） assay and also explored the mechanism of antiproliferation of them. The results show that TH1082 significantly inhibited the proliferation of these cells to different extent. The IC50 values for A375 cells, SMMC cells and MCF-7 cells were 25.38, 48.70 and 76.94 μg/mL at 24 h, respectively. To observe cell morphological changes, acridine orange/ethidium bromide（AO/EB） staining and Hoechest33342/Pl staining were carried out. These results indicate that TH1082 could induced the apoptosis of A375 cells. The apoptotic rates were （9.5±2.09）%, （18.9±2.25）% and （39.5±2.02）%（5, 10 and 20 μg/mL） for A375, SMMC and MCF-7 cell lines, respectively. Further, we determined the activities of caspase-3 and caspase-9 in A375 cells treated with TH1082 at different concentrations（0, 5, 10 and 20 μg/mL） or Z-VAD-FMK（20 μmol/L）, a pan-caspase inhibitor for 24 h. The results show that TH1082 activated caspase-3 and caspase-9, and the activation could be blocked by Z-VAD-FMK. Taken together, these findings indicate that TH 1082 could inhibit the proliferation ofA375 cells via activating caspase-3 and caspase-9.     

Ruthenium Complexes as Promising Candidates against Lung Cancer

Lung cancer is one of the most common malignancies with the highest mortality rate and the second-highest incidence rate after breast cancer, posing a serious threat to human health. The accidental discovery of the antitumor properties of cisplatin in the early 1960s aroused a growing interest in metal-based compounds for cancer treatment. However, the clinical application of cisplatin is limited by serious side effects and drug resistance. Therefore, other transition metal complexes have been developed for the treatment of different malignant cancers. Among them, Ru(II/III)-based complexes have emerged as promising anticancer drug candidates due to their potential anticancer properties and selective cytotoxic activity. In this review, we summarized the latest developments of Ru(II/III) complexes against lung cancer, focusing mainly on the mechanisms of their biological activities, including induction of apoptosis, necroptosis, autophagy, cell cycle arrest, inhibition of cell proliferation, and invasion and metastasis of lung cancer cells.     

In vivo Antimalarial Activity of Andrographis Paniculata Tablets

The formulation of three phytopharmaceutical products of Andrographispaniculata fractions (AP fraction A and B) containing diterpene lactones as an active substance were developed and their antimalarial activities against Plasmodium bergheihas been examined. In vivo antimalarial assay on P. berghei infected mice was carried out by oral administration,twice a dayfor four consecutive days of the AP fractions product, which were Tablet I: wet granulated formula of AP fraction A; Tablet II: wet granulated formula of AP fraction B; Tablet III: solid dispersion formula of AP fraction B.. The results revealed that three phytopharmaceutical products of A.paniculata were inhibited parasite's growth with inhibition range of 70.15% to 80.35%. There was no significant difference of antimalarial activities between Tablet II and III, meanwhile there was significant difference among Tablet I with Tablet II and Tablet III.It was concluded that antimalarial activity depending on raw material form of A. paniculata active substance.     

Synthesis,Docking and Biological Evaluation of Isoquinolonic Acid Derivatives

A series of isoquinolonic acid derivatives（4a-4o） was synthesized via one-pot synthesis for their anti-tumor activity. The structures of all the targeted compounds were confirmed by IH nuclear magnetic resonance （IH NMR） spectrometry and mass spectrometry（MS）. The anti-tumor activities of compounds 4a-4o against MG63（human osteosarcoma cells） and B16-F10（mouse melanoma cells） were examined. To evaluate the antitumor effect of the as-synthesized compounds, we compared the half maximal inhibitory concentration（1C50） of compounds 4a--4o to that of camptothecin（CPT） which appeared to be active against a broad range of human cancers. Among all the compounds, compound 41 shows the most potent biological activity against MG63 cells[IC50=（2.16i0.26） μmol/L] and B16-F10 cells[IC50=（6.95±0.24）μmol/L], thus providing useful information for the antitumor activity and potential practical use of isoquinolonic acid compounds. In addition, we screened out an efficient compound（41） that shows potential inhibit activity against Topoisomerase 1（Topo 1） by docking simulation.     

Synthesis and biological evaluation of 3-(piperidin-4-yl)isoxazolo[4,5-d]pyrimidine derivatives as novel PI3Kδ inhibitors

An efficient synthesis of novel 3-(piperidin-4-yl)isoxazolo[4, 5-d]pyrimidine scaffold has been designed and deveopled. A series of 5-phenylurea derivatives was synthesized using this method. Their cytotoxic activities against breast cancer cell line BT-474 were evaluated by CCK-8 assay. Most of them showed potent anti-proliferative activities, of which compound 20 and 21 exhibited IC₅₀s of 1.565 μmol/L and 1.311 μmol/L, respectively. Furthermore, compound 20 and 21 also showed potent inhibitory activities against PI3Kδ with IC₅₀s of 0.286 μmol/L and 0.452 μmol/L, respectively. These results indicate that these 3-(piperidin-4-yl)isoxazolo[4, 5-d] pyrimidine derivatives are novel antitumor agents through the inhibition of PI3Kδ.     

五味子酯J和五内酯F的分离与结构

从长梗南五味子(Kadsura Lorgipedunculata Finet.et Gagnep)种子中分得2个新化合物: 五味子酯(schisantherin)J(1)和五内酯(schisanlactone)F(2); 4个已知物: 五内酯(Schisanlactone)A、schizandronic acid、表安五酸(epianwuweizic acid)和二甲基去当归酰五味子酯F, 抗癌药理筛选表明, 在体外2对白血病P-388细胞有明显抑制作用。     

Novel 1,3,5-thiadiazine-2-thione derivatives containing a hydrazide moiety: Design,synthesis and bioactive evaluation against phytopathogenic fungi in vitro and in vivo

A series of novel 1,3,5-thiadiazine-2-thione derivatives bearing a hydrazide moiety were designed, synthesized and evaluated for their biological activities against phytopathogenic fungi. The antifungal bioassays indicated that the title compound 5b impressively displayed the obvious selectivity and specificity aganist Rhizoctonia solani (Rs) in vitro and in vivo. The above researches provide a significant reference for the further structural optimization of 1,3,5-thiadiazine-2-thione derivatives bearing a hydrazide moiety as potential fungicides.     

Synthesis and antitumor activity of some new pyrazolo[1,5-a] pyrimidines

New series of pyrazolo[1,5-a]pyrimidine derivatives 7a-i, 11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines, namely colorectal carcinoma (HCT116), prostate adenocarcinoma (PC-3) and liver carcinoma (HepG-2) using MTT cytotoxicity assay at 100 μg/mL. Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells. Whereas, compounds 7d and 11a showed better antitumor activity than the rest of the compounds against both cell lines. A structure-activity relationship (SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data (MS, IR, ¹H NMR and ¹³C NMR) and elemental analysis.     

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。     

杜氏盐藻多糖的高效体积排阻色谱的保留特性及其分析方法的研究

通过对从杜氏盐藻中提取出的不同多糖级分在高效体积排阻色谱柱(Waters Ultrahydragel Linear,7.8 mm i.d.×300 mm,2根串联)上的保留特性的考察及其分离分析条件的优化,建立了高效体积排阻色谱分析盐藻多糖平均相对分子质量及其分布的方法。结果表明:流动相中盐的种类及其浓度、pH值对3种酸性多糖级分(特别是硫酸化多糖级分PD4a)的保留行为有显著影响;在柱温为45 ℃,流速为0.9 mL/min条件下,使用0.1 mol/L的NaAc水溶液作流动相基本上能消除非特异性吸附作用及分子间缔合等因素的干扰,使各多糖级分基本以非缔合状态按立体排除机制保留和分离。在优化的色谱条件下,测得的盐藻多糖5个级分的重均相对分子质量(Mw)分别为1548000,33000,67000,424000,10000;测得的硫酸化多糖级分PD4a的Mw和峰面积的相对标准偏差分别为1.7%和 0.88%(n=5)。     

Synthesis and Biological Activity of Novel Anthranilic Diamides Containing N-Substituted Arylmethylene Moieties

A series of novel anthranilic diamides containing N-substituted arylmethyl moieties was designed and synthesized, in which the bond distance and conjugation pattern between pyrazole and pyridine rings contained in Chlorantraniliprole were changed. Their structures were confirmed by JH NMR, IR, elemental analysis or high resolution mass spectromentry{HRMS）, and the conformation of compound 4d was confirmed by X-ray diffraction. The preliminary bioassay results indicate that all the target compounds exhibited moderate insecticidal activity against oriental armyworm at 200 mg/L and some of them presented favorable antitumor activities against human lung cancer cells（A549）, liver cancer cells（BelT402） and colon cancer celIs（HCT-8） in vitro by microculture tetrazolium（MTT） method, among which compound 6j afforded the best anti-proliferative activity at 5μg/mL.     

Potential Anticancer Activity of the Furanocoumarin Derivative Xanthotoxin Isolated from Ammi majus L. Fruits: In Vitro and In Silico Studies

Ammi majus L., an indigenous plant in Egypt, is widely used in traditional medicine due to its various pharmacological properties. We aimed to evaluate the anticancer properties of Ammi majus fruit methanol extract (AME) against liver cancer and to elucidate the active compound(s) and their mechanisms of action. Three fractions from AME (Hexane, CH₂Cl₂, and EtOAc) were tested for their anticancer activities against HepG2 cell line in vitro (cytotoxicity assay, cell cycle analysis, annexin V-FITC apoptosis assay, and autophagy efflux assay) and in silico (molecular docking). Among the AME fractions, CH₂Cl₂ fraction revealed the most potent cytotoxic activity. The structures of compounds isolated from the CH₂Cl₂ fraction were elucidated using ¹H- and ¹³C-NMR and found that Compound 1 (xanthotoxin) has the strongest cytotoxic activity against HepG2 cells (IC₅₀ 6.9 ± 1.07 µg/mL). Treating HepG2 cells with 6.9 µg/mL of xanthotoxin induced significant changes in the DNA-cell cycle (increases in apoptotic pre-G1 and G2/M phases and a decrease in the S-phase). Xanthotoxin induced significant increase in Annexin-V-positive HepG2 cells both at the early and late stages of apoptosis, as well as a significant decrease in autophagic flux in cancer compared with control cells. In silico analysis of xanthotoxin against the DNA-relaxing enzyme topoisomease II (PDB code: 3QX3) revealed strong interaction with the key amino acid Asp479 in a similar fashion to that of the co-crystallized inhibitor (etoposide), implying that xanthotoxin has a potential of a broad-spectrum anticancer activity. Our results indicate that xanthotoxin exhibits anticancer effects with good biocompatibility toward normal human cells. Further studies are needed to optimize its antitumor efficacy, toxicity, solubility, and pharmacokinetics.     

二肽类膦酸酯衍生物的合成与抗肿瘤活性

为了寻找抗肿瘤活性化合物,以前期研究的含一个氨基酸结构单元的膦酸酯衍生物为基础,设计合成了15个二肽类膦酸酯衍生物(Ⅲa-Ⅲo).采用溴化噻唑蓝四氮唑(MTT)法进行体外抗肿瘤活性测试.结果表明:该类化合物对人肺癌细胞(A-549)、人胃癌细胞(SGC-7901))和人食管癌细胞(EC-109)有潜在增殖抑制作用.其中...     

Capillary gas chromatographic analysis of pyrrolidinedithiocarbamate metal chelates

Pyrrolidinedithiocarbamate (PDTC) chelates of Zn(II), Cu(II), Ni(II), Co(III), Fe(III), Mn(II), Cr(III), and VO(II) were analysed by capillary GC on a DB-1701 column (30 m x 0.25 mm id) with flame ionisation detection (FID). Linear calibrations were attained within "1-30 microg/mL" for Ni(II), Fe(III), Mn(II), Cr(III), Cu(II), and VO(II), and within "2-50 microg/mL" for Co(III) and Zn(II). The limits of detection were in the "150-500 ng/mL" range, corresponding to 15-50 pg amounts reaching the FID system. The optimised method was applied to the determination of Cu(II) and Ni(II) in coins, and that of Zn(II), Cu(II), Ni(II), Fe(III), Mn(II), Cr(III), and VO(II) in pharmaceutical preparations with relative standard deviations within 1.1-5.2%. The results obtained are in good agreement with sewage water samples and the declared values for the pharmaceutical formulations, or with the results of AAS of metal contents in coins, pharmaceutical preparations, and sewage water samples.     

(8R,13R)-8,12,13,17-四氢穿心莲内酯的合成、晶体结构和葡萄糖苷酶抑制活性

设计并合成了新的具有旋光活性的二萜类内酯衍生物2, 并通过NMR, IR, HRMS和X射线单晶衍射等技术分析了其结构和绝对构型.