喜树碱功能化修饰及抗肿瘤活性研究进展

喜树碱是一种重要的天然产物,具有很强的抗肿瘤活性。然而,喜树碱存在水溶性差、在生理条件下易水解而转为无活性的喜树碱羧酸盐等缺陷,限制了其通过静脉注射的临床应用。而对喜树碱的喹啉环、α-羟基内酯环进行功能化修饰可克服上述缺陷。本文就喜树碱结构的功能化修饰及其抗肿瘤活性进行了综述,以期为其他研究人员更快地开发出具有高效、低毒的新型喜树碱类抗癌药物提供参考。     

10-酯基高喜树碱的全合成及抗肿瘤活性研究

以2,8-二氧-3-乙基-6,6-亚乙二氧基-2,3,5,6,7,8-六氢-3-羟基吡喃(5,4-c)中氮茚为起始原料, 经五步反应得到高喜树碱, 羟甲基化后与一系列酸成酯合成了6个10-酯基高喜树碱, 并利用¹H NMR, MS及元素分析对其结构进行了表征. 采用经典的噻唑兰(Thiazoly blue tetrazolium bromide, MTT)法测定了其体外抗肿瘤活性, 活性测试结果表明3个化合物具有比阳性对照药拓扑替康增强的活性.     

10-羟基喜树碱氨基酸缀合物的合成及抗肿瘤活性研究

以10-羟基喜树碱为原料,通过两碳边链链接,合成了一系列10-羟基喜树碱氨基酸缀合物和9-硝基-10-羟基喜树碱氨基酸缀合物.采用CCK-8法测试了合成化合物体外对人口腔鳞癌细胞KB、人肝癌细胞HepG2和小鼠结肠癌细胞C26三组细胞株的增殖抑制活性,结果表明部分目标化合物对所选肿瘤细胞株显示了潜在的抑制活性,其中10-羟基喜树碱氨基酸缀合物的体外活性明显优于9-硝基-10-羟基喜树碱氨基酸缀合物的体外活性.     

5-位烷基化取代的喜树碱衍生物的合成和抗肿瘤活性研究

喜树碱(Camptothecin,CPT)是美国化学家Wall和Wani在1966年首先从中国珙桐科植物喜树(Camptothecaacuminata)中提取出来的一种生物碱.试验表明它对许多实体瘤有抗肿瘤活性.药物学家对喜树碱分子的结构修饰,大多数集中在喜树碱的A,B和E环上.喜树碱的C环上5-位取代往往降低活性.我们在制备喜树碱烷基化衍生物过程中发现,喜树碱及其衍生物在碳酸钾和活泼溴代烷作用下得到5-位烷基化产物,用不同的溴代烷分别得到单取代或双取代产物.我们合成的5-位烷基化的喜树碱衍生物经过人肿瘤细胞(KB,KB/VCR,A549,HCT-8,Bel7402,A2780)的体外筛选实验,表明这一类化合物细胞毒性显著降低甚至丧失,这可能是因为取代基的空间位阻作用影响了D环羰基和受体的结合.     

类查耳酮氟喹诺酮衍生物的合成及抗肿瘤活性

基于α,β-不饱和酮的结构特征,设计合成了12个新的类查尔酮氟喹诺酮目标化合物5a～5l,其结构经元素分析和光谱数据确证,评价了它们对SMMC-7721、Capan-1和HL60三种癌细胞株的体外抗增殖活性。目标化合物的抗肿瘤活性显著高于母体化合物1,其中含氯苯基的化合物5k的活性与对照抗肿瘤药阿霉素相当。具有α,β-不饱和酮结构片段的类查尔酮氟喹诺酮化合物的抗肿瘤活性值得进一步研究。     

抗癌药物喜树碱衍生物的研究

喜树碱是一种天然抗癌药物,通过对喜树碱20位羟基的修饰和对喜树碱E环扩环,来提高该类化合物的活性并减小毒性,起到更好的治疗效果。简单介绍喜树碱衍生物的研究现状及其未来的发展趋势。     

松香烷内酯型大戟二萜化合物的研究进展

松香烷内酯是大戟属植物中提取的一种典型二萜类化合物, 其基本结构为四环二萜, 有多种药理活性, 特别是有较强的抗肿瘤活性. 对国内外已经报道的松香烷内酯型大戟二萜化合物结构进行了归纳分类, 同时综述了近年来国内外文献对此类化合物的抗肿瘤药理活性、作用机制以及合成研究的进展情况, 总结和讨论了此类化合物的构效关系, 评述了这类化合物作为抗肿瘤药物的开发潜力, 提出了目前存在的问题与不足, 并对其发展前景和研究方向做出了预测和展望.     

合成化合物动物体内抗肿瘤实验方法研究进展

进行了动物体内抗肿瘤活性研究的多为天然药物,但其来源有限;虽然用于抗肿瘤研究的合成化合物种类较多,但对于其在动物体内抗肿瘤研究又相对偏少,所以,合成化合物抗肿瘤体内研究已经成为研究热点之一。本文对合成化合物抗肿瘤作用机制、体内肿瘤模型建立方法和体内抑瘤实验研究等方面的研究进展进行了评述,并通过大量实验数据对合成化合物毒性评价方法、抑瘤基本观察指标测定、氧化损伤相关酶活力的测定方法、组织病理学评价方法等体内抑瘤实验的评价标准和方法进行了详细总结,提出了合成化合物在体内动物抗肿瘤实验研究方法中亟待解决的问题,为新型抗肿瘤合成化合物体内药学活性研究提供有益的参考。     

氯硝柳胺衍生物的合成及抗肿瘤活性研究

以氯硝柳胺为起始原料,经醚化、亲核取代反应得到目标化合物,采用MTT法考察所合成化合物对人类乳腺癌细胞(MDA-MB-231)和人类胰腺癌细胞(ASPC-1)的体外抗肿瘤活性。合成了5个氯硝柳胺衍生物,其结构均经IR、1H-NMR、13C-NMR和MS确证。初步的体外抗肿瘤活性结果显示目标化合物9b和9c的抗肿瘤活性强于阳性对照药,其中化合物9b的活性对所测两种肿瘤株的抑制活性均强于阳性对照药,展现出较强的应用前景。     

黄酮类化合物结构修饰及抗肿瘤活性研究进展

我国天然药物和中药资源丰富,种类繁多,可作为先导化合物进行修饰以提高可成药性。其中,黄酮类化合物是自然界中一种常见的天然多酚类化合物,在抗肿瘤方面具有其独特的生物活性;对其进行结构修饰与改造,可提高黄酮类化合物的生物利用度和抗肿瘤活性。本文通过查阅并整理近几年国内外的黄酮类化合物的相关文献,对黄酮类化合物的母核位点进行结构修饰与改造所得的101个黄酮类衍生物及其抗肿瘤活性及作用机制进行综述,同时讨论了构效关系,以期为黄酮类衍生物的结构修饰和抗肿瘤研究提供参考和帮助。     

Apoptosis of Human Gastric Carcinoma SGC-7901 Induced by Deoxycholic Acid via the Mitochondrial-Dependent Pathway

The study aimed to evaluate the effects of deoxycholic acid (DCA) on human gastric carcinoma cell lines and to explore its mechanisms. In the present study, effects of DCA on SGC-7901 cell growth, cell cycle, and apoptosis were investigated by MTT assay, inverted microscopy, fluorescence microscopy, PI single- and FITC/PI double-staining flow cytometry, and western blotting. The study have revealed that DCA significantly inhibited the growth of SGC-7901 cells in a dose- and time-dependent manner and arrested cell cycle at G0/G1 phase. SGC-7901 cells showed typical apoptotic morphological changes after treated with DCA for 48 h. The intensity of typical apoptosis pattern- “ladders” formed by DNA in fragments of multiples of 200 base pairs was also observed. Apoptosis of SGC-7901 cells induced by DCA were associated with collapse of the mitochondrial membrane potential. DCA treatment could also increase the ratio of Bax to Bcl-2 in SGC-7901 cells. Meanwhile, the expression of p53, cyclinD1, and c-Myc were changed after DCA treatment. These results suggest that DCA induces apoptosis of gastric carcinoma cells through an intrinsic mitochondrial-dependent pathway, and the increase in the Bax/Bcl-2 ratio and collapse of the mitochondrial membrane potential may play important roles in DCA-induced apoptosis of gastric carcinoma cells.     

6-氯-4-哌嗪基喹唑啉缩氨基硫脲类化合物的合成及体外抗肿瘤活性

以5-氯-2-氨基苯甲酸和甲酰胺为起始原料,经环化、氯化、取代和缩合反应,合成了3个未见文献报道的含哌嗪的喹唑啉衍生物5a~5c。 其结构用1H NMR、13C NMR、ESI-MS及IR测试技术进行了表征。 采用MTT法测试了化合物5a~5c对人胃癌SGC-7901、人口腔表皮样癌KB和人纤维肉瘤HT-1080的体外抗肿瘤活性。 结果表明,化合物5a~5c对人胃癌SGC-7901和人纤维肉瘤HT-1080有弱的抑制活性,而对人口腔表皮样癌KB无明显抑制活性。     

熊果酸C-3,C-28位衍生物的合成及其抗肿瘤活性研究

以天然产物熊果酸为原料,经过氧化、酰化、酯化等反应合成了11个未见报道的熊果酸衍生物,其结构经过MS、1H NMR及元素分析确定。以氟尿嘧啶和吉非替尼为阳性对照药,经MTT法对A549和SGC-7901细胞进行初步体外抗肿瘤活性研究。结果表明,目标化合物对两种细胞株的抑制率均明显高于母体化合物,且化合物4b和5a的抑制效果高于阳性对照药,值得进一步研究。     

基于双向浓度梯度的微流控芯片系统对 肿瘤细胞侵袭能力的多重分析

利用微流控芯片易于模拟体内生理环境、 流体控制精确及易于集成等优势, 将基于扩散原理的浓度梯度形成结构与经典的圣诞树形浓度梯度发生器相集成, 建立了在垂直和水平方向上形成连续、 双向浓度梯度的微流控芯片系统, 采用该系统对不同类型细胞(HEK-293, MCF-7, SGC-7901)的侵袭力进行了定量分析; 通过在垂直方向上施加血清浓度梯度, 在水平方向上施加抗肿瘤药物十字孢碱浓度梯度, 分析了在连续药物浓度作用下的人胃癌SGC-7901细胞侵袭能力被抑制的情况, 同时观察并定量评价了伴随细胞侵袭力变化过程中细胞增殖能力受抑制的情况. 研究结果表明, 该系统可形成稳定的双向物质浓度梯度; 在血清浓度梯度存在情况下, 伴随十字孢碱浓度梯度的升高, 肿瘤细胞侵袭(P<0.0001)和增殖能力(P<0.001)均呈现浓度依赖性的连续降低. 建立的双向浓度梯度微流控芯片系统可用于评价复杂环境对细胞的多重影响, 也为研究细胞间相互作用、 多种药物联用及药物筛选等提供了良好的研究平台.     

Cytotoxic Activity of Some Novel Dicoumarin Derivatives in vitro

Some novel dicoumarin derivatives, triethylene-glycol dibenzo[5,6] coumarin-3-carboxylate(1a),PEG (600) dibenzo[5,6]coumarin-3-carboxylate(1b), triethylene-glycol di[7-(N,N'-diethylamino)]-coumarin-3-carboxylate(2a), were synthesized. The cytotoxic effect of these compounds, along with benzo[5,6]coumarin-3-carboxylic acid(1) and 7-(N,N'-diethylamino)-coumarin-3-carboxylic acid(2), against the SGC-7901 cell lines were determined by Sulforhodamine B(SRB) assay. The preliminary cytotoxicity screening process r...     

6,7-二甲氧基-4-哌嗪喹唑啉缩氨基硫脲衍生物的合成及体外抗肿瘤活性研究

以4,5-二甲氧基-2-氨基苯甲酸和醋酸甲眯为起始原料,经环化、氯化、取代和缩合四步反应,设计、合成了六个未见文献报道的含有缩氨基硫脲的喹唑啉衍生物4a～4f,其结构用1H NMR,13C NMR,ESI-MS,IR及元素分析测试技术进行了表征.采用MTT法测试了化合物4a～4f对人胃癌SGC-7901、人口腔表皮样癌KB和人纤维肉瘤HT-1080的体外抗肿瘤活性.初步的测试结果表明,化合物4a和4f对HT1080表现出显著的抗肿瘤活性.     

Synthesis,characterization and in vitro antitumor behavior of a vanadium(V) complex with 4′-(3-methoxyphenyl)-2,2′:6′2″-terpyridine

A dioxovanadium(V) complex, [VO₂(moptpy)](ClO₄) (1, moptpy = 4′-(3-methoxyphenyl)2,2′:6′2″-terpyridine), was synthesized and characterized by elemental analysis, ESI-MS, UV–vis, IR, and ¹H, ¹³C, and ⁵¹V NMR. The cytotoxicity in vitro of 1 was evaluated against cancer cell lines HepG-2 (hepatocellular carcinoma), SGC-7901 (gastric carcinoma), SiHa (cervical cancer), BEL-7402 (hepatocellular), and rat PC-12 (pheochromocytoma) by the MTT method. The results demonstrated that 1 exhibits superior anticancer activity in vitro with much lower values of 50% inhibitive concentration (IC₅₀) against the selected cell lines than cisplatin, and 1 shows the highest cytotoxic activity toward SGC-7901 cells (IC₅₀ = 1.3 ± 0.1 μM) among the selected cell lines. A series of cellular morphological and staining experiments were carried out, and the results indicated that 1 can effectively induce apoptosis of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction pathway. In addition, cellular incorporation and cell cycle analysis were also performed, and it was concluded from the experimental observations that 1 can efficiently enter into the cell nuclei, and the complex inhibits cell growth in SGC-7901 cell at G0/G1 phase.     

光激发纳米TiO2对胃癌SGC-7901细胞的杀伤作用

探讨了光激发纳米TiO2对胃癌SGC-7901细胞的杀伤作用, 考察了在不同纳米TiO2浓度及不同光照时间下纳米TiO2的抑瘤效果, 并探讨了抑瘤机制. 结果表明, 光激发纳米TiO2对胃癌SGC-7901细胞具有明显的抑制作用, 其过程类似一级反应的动力学规律; 当纳米TiO2浓度为300 μg/mL时, 对胃癌SGC-7901细胞表现出较强的杀伤效果, 其主要表现形式有两种, 即细胞坏死和细胞凋亡, 是由光激发条件下, 纳米TiO2表面产生的活性氧组分对肿瘤细胞的有效杀伤所致.     

Two new triterpenoids from Gypsophila oldhamiana

Two new triterpenoids (1–2) were isolated and elucidated from the roots of Gypsophila oldhamiana, together with four known triterpenoids (3–6). Their structures were identified to be 3β-hydroxyolean-13(18)-ene-23, 28-dioic acid (1), 3β, 12α-dihydroxy-23-carboxyolean-28, 13β-olide (2), 3β, 16α-dihydroxy-23-oxoolean-13(18)-en-28-oic acid (3), gypsogenin (4), quillaic acid (5) and gypsogenic acid (6) by spectral methods. All compounds were tested for their cytotoxicities against human tumour cell lines (lung cancer H460 and gastric cancer SGC-7901) and for their antiangiogenic effects using a zebra fish model. All compounds showed interesting antiangiogenic activities and the significant cytotoxicities against H460.     

Biosynthesis, characterization and biological evalutation of Fe(III) and Cu(II) complexes of neoaspergillic acid, a hydroxamate siderophore produced by co-cultures of two marine-derived mangrove epiphytic fungi

A hydroxamate siderophore, neoaspergillic acid (1), and a red pigment, ferrineoaspergillin (2) which is an Fe(III) complex of 1, were produced by co-cultures of two epiphytic fungi from a rotten fruit of the mangrove Avicennia marina from the South China Sea, and a new Cu(II) complex of 1, designated as cuprineoaspergillin (3), was also prepared by treatment of 1 with cupric acetate. All the compounds (1-3) were characterized by physical and chemical techniques, including 1H NMR, ESIMS, and photoelectron energy spectra. In the bioassays, compounds 1-3 showed significant inhibitory activities against selected Gram-positive and Gram-negative bacteria, and compound 1 also exhibited moderate inhibitory activities against human cancer cell lines SPC-A-1, BEL-7402, SGC-7901 and K562.