治疗艾滋病的药物组合物,其制备方法及其用途

本发明提供一种治疗艾滋病的药物组合物，其中含有治疗艾滋病有效量的式(I)化合物联苯环辛二烯类木脂素(+)-戈米辛 K3[(+)-gomisin K3]及可药用载体和/或赋形剂。该药物组合物通过抑制逆转录酶和蛋白酶活性的作用机制，从而达到抑制HIV-1病毒的增殖。本发明同时给出了该药物组合物的制备方法，及其在制备逆转录酶抑制剂药物和在制备抗艾滋病药物中的应用。

光动力疗法抑制人免疫缺陷病毒复制的实验研究

通过对人免疫缺陷病毒复制过程的抑制作用研究，探索光动力疗法(PDT)在艾滋病防治中的潜在价值。使 用不同稀释浓度的光敏剂血卟啉单甲醚(HMME)和亚甲蓝(MB)分别与人免疫缺陷病毒HIV一1Ⅲs或宿主细胞 MT4，C8166或H9／HIV-IⅢB孵育2 h。以波长630 nm能量密度0．3 J／cm2的半导体激光进行照射。继续孵育若干 小时后，用噻唑蓝(MTT)比色法检测细胞存活率或合胞体计数，同时收集培养上清液用ELISA法检测HIV-I p24 抗原。结果表明，光动力疗法能显著抑制人免疫缺陷病毒诱导的细胞一细胞融合(HMME-PDT抑制率64．68％， MB-PDT抑制率61．56％)和病毒一细胞融合(HMME—PDT抑制率85％，Mt}PDT抑制率73．64％)，并对游离病毒 有很强的杀伤作用，最高可达到100％。光动力疗法不能抑制慢性感染期和急性感染2 h后病毒的复制过程。可 见光动力疗法对游离病毒和病毒感染诱导的膜融合有显著抑制作用，有可能为艾滋病的防治提供一种新的方法。

恒河猴TRIM5α的组织分布及不同刺激促进PBMC中TRIM5α转录水平的上调

TRIM5α(tripartite motif protein 5-alpha)蛋白是恒河猴体内一种非常重要的限制因子,能抑制人免疫缺陷病毒(HIV-1,human immunodeficiency virus type 1)、马感染性贫血病毒(EIAV, equine infectious anemia virus)和猫免疫缺陷病毒(FIV, feline immunodeficiencyvirus)等逆转录病毒的复制.恒河猴TRIM5α的组织分布以及在受到外界刺激时TRIM5α mRNA表达量的变化研究还未见报道.本研究从中国恒河猴的各组织中提取总RNA,以β-actin基因作为内参照,通过半定量RT-PCR检测各组织中TRIMSα mRNA的表达.选择HIV-GFP-VSVG假病毒感染外周血单核细胞(peripheral blood mononuclear cell,PBMC),非特异性刺激剂--佛波脂(Phorbol myfismte acetate,PMA)+离子霉素(ionomycin,Ion)及CD28抗体+CD49d抗体分别共刺激恒河猴PBMC,研究不同刺激对恒河猴TRIM5α mRNA表达水平的影响.结果表明:TRIM5α mRNA表达于所研究的恒河猴21种组织中,免疫系统和泌尿生殖系统组织中表达量最高,而神经系统组织,如大脑、脊髓中表达较少,其他组织中未见明显的表达差异;HIV-GFP-VSVG感染和用PMA+Ion、CD28抗体+CD49d抗体分别共刺激PBMC能促进PBMC中TRIM5α mRNA的转录水平的上调.

Chemical Constituents from Fruit Hulls of Garcinia mangostana ( Cuttiferae

从山竺(Garcinia mangostana)果壳中分离得到6个化合物,通过MS,1D 1NMR以及与文献对照鉴定它们为4个(口山)酮类化合物:α-mangostin(1),β-mangostin(2),γ-mangostin(3),5,9-dihydroxy-8-methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-2H,6H-pyrano-[3,2-b]-xanthen-6-one(4),以及表儿茶素(epicatechin,5)和一个双苄类化合物egonol(6).其中化合物5和化合物6为首次从该植物中分离得到.对化合物1～5进行抗HIV-1 RT活性筛选结果表明,化合物2和化合物5在浓度200 μg/ml的条件下,其对HIV-1 RT抑制率分别为41.97%和47.72%;同一实验结果显示化合物1,3和4没有抑制HIV-1 RT作用.

New rotenoids from roots of Mirabilis jalapa

Four new rotenoids named mirabijalone A-D-1) (1-4), together with 9-O-methyl-4-hydroxyboeravinone B (5), boeravinone C (6) and F (7), and 1,2,3,4-tetrahydro-1-methylisoquinoline-7,8-diol (8), were isolated from the roots of Mirabilis jalapa. The structures of these compounds were determined on the basis of their HR-EI-MS, IR, UV, H-1- and C-13-NMR (DEPT). and 2D NMR (HMQC, HMBC, NOESY) data. Among them, 1,2,3,4-tetrahydro-1-methylisoquinoline-7,8-diol (8) showed a 48% inhibition against HIV-1 reverse transcriptase at 210 mug/ml.

4-Benzyl-5-ethyl-2-(2-furylcarbonylmethylsulfanyl) pyrimidin-6(1H)-one

The title compound, C19H18N2O3S, shows favourable activity against HIV-1. The phenyl ring is twisted with respect to the pyrimidine ring by 61.56 (9)degrees. Intermolecular N-H center dot center dot center dot O and C-H center dot center dot center dot O

Chemical Constituents from the Leaves and Stems of Schisandra lancifolia

A new nortriterpenoid, 20-hydroxymicrandilactone D (1) and a novel lignan glycoside, lancilignanside A (2) were isolated from leaves and stems of Schisandra lancifolia, together with three known nortriterpenoids (3-5) and nine known phenolics (6-14). The structures of new compounds 1 and 2 were determined by detailed analysis of their 1D and 2D NMR spectra, and chemical evidences. In addition, compounds 1-2, 6-7, and 9-11 showed anti-human immunodeficiency virus (HIV)-1 activities with 50% effective concentration (EC50) in the range of 3.0-99.0 mu g/ml. Compound 12 was not bioactive in this assay with EC50 more than 200 mu g/ml.

Chemical Constituents from the Leaves and Stems of Schisandra rubriflora

Six new nortriterpenoids, schirubridilactones A-F (1-6). as well as 14 known compounds, were isolated from the leaves and stems of Schisandra rubriflora. The Structures of 1-6 were elucidated oil the basis of spectroscopic methods including HSQC, HMBC, H-1-H-1 COSY, and ROESY NMR experiments. The relative stereochemistry of I was confirmed through single-crystal X-ray analysis. In addition, compounds 1-6 showed anti-HIV-1 activity with EC50 values in the range 14.3-80.8 mu g/mL and Selectivity indices in the range 2.2-9.0.

Highly Functionalized Daphnane Diterpenoids from Trigonostemon thyrsoideum

Trigonothyrins A-C (1-3), which are highly functionalized daphnane diterpenoids, were isolated from the stems of Trigonostemon thyrsoideum. Compounds 1-3 represent the first examples of daphnanes with an oxygen-bridged four-membered-ring system, and a linkage mode of 12,13,14-orthoester. Compound 3 was observed to inhibit HIV-1 induced cytopathic effects. The EC50 value was 2.19 mu g/mL, and the therapeutic index (TI) was more than 90.

一种质粒及其构建方法和在艾滋病毒载量测定上的应用

一种质粒及其构建方法和在艾滋病毒载量测定上的应用，属艾滋病防治领域。质粒为pSPgag737/JM109 CGMCC NO.0486。构建方法是将HIV－1前病毒DNA进行Sal I/sacI双酶切，与被同样双酶切的pSP64Poly(A)质粒发生粘性末端连接，得到含有HIV－lgag基因片断的pSPgag737重组质粒，转化至JM109感受态细胞，经酶切/PCR鉴定，得到阳性克隆子。体外转录阳性克隆子，获得病毒载量定量测定的RNA外参照，将PCR技术与Kodak电泳图谱分析系统相结合，建立了HIV感染者和艾滋病人血浆病毒载量的定量测定方法。本发明操作简单，价格便宜，特异性好，灵敏度高，可重复性好，作为艾滋病的科学研究与防治的工具。

树鼩CXCR4cDNA的克隆和序列分析

　目的　获得树　CXCR4 的cDNA 序列,探讨其是否可以支持HIV-1 病毒和细胞的结合。方法　设计 相应的引物, 用RT- PCR ,基因克隆,DNA 序列分析技术。结果　获得了全长为1059bp 树　CXCR4 (tsCXCR4) 基因 的cDNA。发现其核苷酸序列与人的CXCR4 (hCXCR4) 基因的cDNA 有9218 % 的相似性,由此推导出的氨基酸序列 有9619 % 相似性。与hCXCR4 功能相关的关键位点完全相同,tsCXCR4 的N 端第7 和12 位点为酪氨酸,第14、15 和 32 位点为谷氨酸,胞外环第183 ,188 为精氨酸, 第193、262 位点以及跨膜区97 位点为天冬氨酸。结论　树　的CX2 CR4 很可能会作为HIV-1 的辅助受体。　

树ju免疫细胞体外感染Ⅰ型人免疫缺陷病毒的实验研究

报告以不同的HIV-1病毒株体外感染树ju免疫细胞的实验研究,结果表明树ju的这些免疫细胞在体外未能感染上HIV-1,可能的原因是树ju的这些免疫细胞的HIV-1受体(CD4)和辅助受体(CCR5或CXCR4)与人的免疫细胞差别较大。

树鼩细胞周期蛋白T1 cDNA的克隆和序列分析

树鼩细胞不能感染 HIV-1, 但支持 HIV-1进入靶细胞后的转录, 可能是因为树鼩细胞周期蛋白T1(tsCycT1)能结合HIV-1的 Tat 蛋白. 通过设计引物, 用 RT-PCR 技术, 获得全长为2175bpts CycT1 基因的cD NA. 其核苷酸序列与人的 CycT1(hCycT1) 基因的 cDNA 有92.6%的相似性; 由此推导出的氨基酸序列有94.1%相似性. 其中, hCycT1 和 tsCycT1 氨基端的1～272个氨基酸的相似性高达98.8%, 氨基酸第261位点为半胱氨酸. 这些结果提示, tsCycT1 会和 HIV-1 的 Tat 结合, 形成高亲和的、锌依赖的复合物, 支持 HIV-1转录。

Effects of testosterone undecanoate as a male contraceptive candidate on rat immunological features

Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety of TU and to understand whether long-term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32-week TU-treated phase at the dose of 20 mg TU/kg body weight and a 24-week recovery phase. The reproductive and immunological parameters of 4-6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU-treated group: the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU-treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long-term supraphysiological TU injection did not obviously affect the examined rat immunological parameters.