紫苏籽皮提取物的自由基清除能力及抗癌活性

探讨紫苏籽皮提取物(PSCE)的体外自由基清除能力及其抗癌活性。结果表明,以DPPH自由基和羟基自由基清除实验检测自由基清除能力。MTT法和平板克隆形成实验分别检测体外抗癌活性。PSCE具有较好的自由基清除能力,对DPPH自由基和羟基自由基的半清除剂量(IC50)分别为105.53μg/mL和269.65μg/mL。同时,PSCE对A375SM人黑色素瘤细胞的增殖抑制作用呈浓度和时间依赖关系。     

细胞毒素类抗癌药物的研究进展

综述了近年来细胞毒素类抗癌药物的研究概况,根据作用机制重点介绍了几类细胞毒素类抗癌药物的合成和结构特点,并对其化学合成方法进行了评价。     

Precise Molecular Engineering of Photosensitizers with Aggregation‐Induced Emission over 800 nm for Photodynamic Therapy

Owing to efficient singlet oxygen (¹O₂) generation in aggregate state, photosensitizers (PSs) with aggregation‐induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high ¹O₂ generation efficiency, strong molar absorption in long‐wavelength range and near‐infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short‐wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation‐induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high ¹O₂ generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8 , which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in ¹O₂ generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application.     

新型钯（Ⅱ）抗肿瘤配合物的合成（Ⅱ）

合成了２个邻菲别罗啉衍生物,咪唑并「ｆ」邻菲史啉和２－苯基咪唑「ｆ」邻菲罗啉。以上述物质作为新的配位剂,与四氯合钯酸钾反应制得新型钯抗肿瘤配合物,即二氯;咪唑并「ｆ」邻菲罗啉合钯及二氯．苯基咪唑并「ｆ」邻菲罗啉合钯。合成的钯配合物经红外光谱,元素分析和测定摩尔电导等手段进行了表征。     

苦参碱脂质体的研究

对苦参碱脂质体的制备工艺进行了研究，并测定了包封率、渗漏率等脂质体的质量指标。以包封率为指标，优选了苦参碱脂质体的最佳制备工艺条件，结果表明：逆相蒸发法制备的脂质体包封率可达50、08％。抗肿瘤实验进行了3个剂量组对小鼠S180的抗瘤效应，结果显示，苦参碱脂质体中剂量组对小鼠S180抗瘤效应最好，对小鼠EAC亦有明显的抗肿瘤作用。     

来曲唑合成的研究

对抗癌药物来曲唑的合成方法进行了研究,以1-(4-氰基苄基)-1H-1,2,4-三氮唑为原料,分别与对氟苯腈或对氯苯腈在强碱环境中发生亲核取代反应,合成了目标产物,产率分别达到了70%和59%,并测试了产品熔点和红外光谱。以与对氟苯腈相比,对氯苯腈便宜易得,因此以1-(4-氰基苄基)-1H-1,2,4-三氮唑与对氯苯腈制备来曲唑的路线有工业化生产的价值。     

雷公藤红素对人肝癌细胞Hep3B中HIF-1α表达的影响

为探讨雷公藤红素对人体肝癌细胞Hep3B中缺氧诱导因子（HIF-1a）活化的影响,利用氯化钴（CoCl2）模拟肝癌细胞缺氧模式,采用双荧光素酶报告基因法检测雷公藤红素对HIF-1α的转录活性,蛋白免疫印迹实验检测雷公藤红素对HIF-1α蛋白质的表达水平,RT-PCR检测雷公藤红素对HIF-1α下游靶基因血管内皮生长因子（VEGF）mRNA的表达水平,电泳泳动度移动分析（EMSA）检测雷公藤红素对HIF-1αDNA的结合能力.结果显示：雷公藤红素呈剂量依赖性抑制了HIF-1α蛋白质的表达水平,降低了肝癌细胞中VEGFmRNA的表达水平并有效抑制了HIF-1α蛋白的DNA结合能力.这表明,雷公藤红素可以抑制肝癌细胞中HIF-1α的活性,这可能是其抗肿瘤的机理之一.     

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

A novel and straightforward synthesis of highly substituted isoquinoline‐5,8‐dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag₂CO₃ promoted, 1,3‐dipolar cycloaddition of C‐heteroaryl‐N‐aryl nitrilimines and substituted isoquinoline‐5,8‐diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC₅₀ values as low as 2.5 μm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells.     

Design,Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents

To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized according to the neoglycosylation approach. The structures of all the products were elucidated by NMR analysis, and the stereochemistry of C20-MeON-pregnenolone was confirmed by crystal X-ray diffraction. The compounds′ cytotoxicity on five human cancer cell lines was evaluated using a Cell Counting Kit-8 assay, and structure–activity relationships (SAR) are discussed. 2-deoxy-d -glucoside 5 k displayed the most potent antiproliferative activities against HepG2 cells with an IC₅₀ value of 1.5 μM. Further pharmacological experiments on compound 5 k on HepG2 cells revealed that it could cause morphological changes and cell-cycle arrest at the G0/G1 phase and then induced the apoptosis, which might be associated with the enhanced expression of high-mobility group Box 1 (HMGB1). Taken together, these findings prove that the neoglycosylation of steroids could be a promising strategy for the discovery of potential antiproliferative agents.     

Synthesis,Anticancer Activity,Structure-Activity Relationship and Mechanistic Investigations of Falcarindiol Analogues

Forty samples of optically active falcarindiol analogues are synthesized by using the easily available C2 symmetric (R)- and (S)-1,1’-binaphth-2-ol (BINOL) in combination with Ti(OⁱPr)₄, Zn powder and EtI. Their anticancer activities on Hccc-9810, HepG2, MDA-MB-231, Hela, MG-63 and H460 cells are assayed to elucidate their structure-activity relationships. These results showed that the falcarindiol analogue (3R,8S)- 2 i with the terminal double bond has the most potent anti-proliferation effect on Hccc-9810 cells with IC₅₀ value of 0.46 μM. The falcarindiol analogue (3R,8S)- 2 i can induce obvious Hccc-9810 cell apoptosis in a concentration-dependent manner by Hoechst staining and flow cytometry analysis. The proposed mechanism suggests that the falcarindiol analogue (3R,8S)- 2 i increases LDH release and MDA content, and reduces the levels of SOD activity, which lead to the accumulation of oxidative stress and induce apoptosis in Hccc-9810 cells.