姜黄素衍生物FM0817体外抗肿瘤活性研究

目的对比研究姜黄素衍生物FM0817与姜黄素对9株体外培养肿瘤细胞的增殖抑制作用。方法应用MTT法检测黄素衍生物FM0817与姜黄素耐9株体外培养肿瘤细胞的增殖抑制率。结果黄素衍生物FM0817与姜黄素对9株肿瘤细胞Ic50平均值分别为1．95μg·mL^-1和10．84μg·mL^-1,FM0817对多种肿瘤细胞的增殖抑制作用明显强于其母核姜黄素。结论姜黄素衍生物FM0817具有较强的体外抗肿瘤活性,有进一步开发研究的前景。     

孔石莼多糖及其硫酸酯化衍生物抗肿瘤活性的体外实验研究

目的研究孔石莼多糖(U)及其硫酸酯化衍生物(HU)对不同肿瘤细胞株生长的影响。方法利用体外细胞培养模型,应用CCK-8法分析孔石莼多糖U及其硫酸酯化衍生物对不同肿瘤细胞生长的影响。结果孔石莼多糖U及其硫酸酯化衍生物HU对人肝癌细胞HepG2、人肺癌细胞SPC-A-1、人胃癌细胞CDX2、人乳腺癌细胞MDA-MB-231均具有一定的抑制作用,但作用又有明显差异。对孔石莼多糖(U)进行硫酸酯化衍生化后增强了对HepG2、SPC-A-1、CDX2及MDA-MB-231肿瘤细胞的抑制作用。结论孔石莼多糖(U)及其硫酸酯化衍生物(HU)对不同肿瘤细胞生长具有一定的抑制作用,硫酸酯化孔石莼多糖(HU)对肿...     

1,3-丁二酮类衍生物对S-180肉瘤细胞生长抑制作用体外实验研究

目的观察1,3-丁二酮类衍生物对S180肿瘤细胞生长的影响,为进一步的研究提供依据。方法细胞增殖程度采用MTT比色法。结果 1,3-丁二酮衍生物B具有较强的抑制S180细胞增殖的作用;1,3-丁二酮衍生物A对S180细胞增殖抑制作用较弱。结论 1,3-丁二酮衍生物B对小鼠S180肿瘤细胞体外增殖有明显抑制作用。     

姜黄素对人卵巢癌裸鼠皮下移植瘤生长的影响

目的　探讨姜黄素对人卵巢癌细胞株 HO 8910 裸鼠皮下移植瘤生长的影响。方法　1×107 个HO 8910细胞接种于裸鼠皮下,待瘤长成约为 10 mm×10 mm×10 mm时,随机分成对照组和治疗组,对照组给予RPMI 1640 4 ml/kg、治疗组分别给予50、100 mg/kg姜黄素腹腔注射治疗5d后,计算移植瘤的体积、瘤重、抑瘤率;瘤组织标本分别进行 HE染色病理检查,电镜和流式细胞仪检测。结果　姜黄素对移植瘤的生长有明显抑制作用,低剂量组和高剂量组的抑瘤率分别达53 .08%和70 .47%,病理、电镜和流式细胞仪检测瘤组织标本均提示经姜黄素治疗后的肿瘤细胞发生了凋亡。结论　姜黄素对人卵巢癌移植瘤的生长具有抑制作用。     

姜黄素衍生物FM0807抗肿瘤活性的研究

目的 研究姜黄素衍生物FM0807的抗肿瘤活性.方法 采用四甲基偶氮唑蓝(MTT)法检测FM0807对多种肿瘤细胞生长的抑制作用,并计算IC50;建立S180小鼠移植肿瘤模型并进行体内实验,观察尾静脉和口服两种途径给予FM0807后体内抗肿瘤效果.结果体外抗肿瘤研究表明,FM0807对CA46、HELA、SGC7901...     

姜黄素及其衍生物抗菌抗炎作用研究进

近年来随着抗生素的不合理使用,出现了越来越多的耐药菌,多重耐药菌已成临床感染性疾病治疗的难题,尤其是对于儿童患者。 研发新型抗菌药物阻止耐药菌的产生及传播已迫在眉睫。 姜黄及其多酚类化合物姜黄素具有广谱抗菌抗炎作用,近年来受到广泛关注。 研究证实,姜黄素及其衍生物对细菌的生长繁殖有抑制作用,并能通过与体内不同分子靶标相互作用在细菌介导的感染性疾病中发挥重要作用。     

姜黄素体外诱导肿瘤细胞凋亡机制的研究及进展

姜黄素是从姜黄类植物中提取出来的一种可食用植物多酚,现已被广泛用做食品佐味,1985年印度的学者Kuttan[1]等首次提出姜黄素具有抗肿瘤作用,至今大量实验证实,姜黄素对多种肿瘤细胞具有抑制生长和诱导凋亡的作用。众多实验证明,姜黄素具有确切的抗肿瘤活性作用,其抗癌谱较广,毒副作用小,是一种具有广泛应用前景的抗癌新药,目前已进入了临床前的毒理试验阶段。姜黄素诱导肿瘤细胞凋亡的途径是多元的,其中,诱导肿瘤细胞凋亡的机制受到了人们的广泛关注。对不同类别肿瘤,其抗肿瘤机制也各不相同,     

6-(4-氨基苯基)-2,3,4,5-四氢哒嗪-3-酮衍生物的合成及生物活性

目的合成6-(4-氨基苯基)-2,3,4,5-四氢哒嗪-3-酮结构的衍生物,探讨其生物活性.方法对6-(4-氨基苯基)-2,3,4,5-四氢哒嗪-3-酮进行结构修饰,考察此类化合物对心血管系统和肿瘤细胞生长两方面的作用.结果设计并合成了2个系列共8个新化合物,所有新化合物结构均经IR、1H-NMR、MS及元素分析确证;8个目标化合物对大鼠离体心房肌收缩频率影响较小,而正性肌力作用明显,其中化合物I d和Ⅱa活性较高;在体外对肿瘤细胞(人肺癌细胞A549、人低分化胃腺癌细胞BGC-823、人原髓细胞白血病细胞HL-60和人肝癌细胞SMMC-7721)的生长具有不同程度的抑制作用,且对HL-60的抑制作用具有一定的专一性,化合物Ⅰ b和Ⅱc对人肺癌细胞A549的抑制作用较强.结论6-(4-氨基苯基)-2,3,4,5-四氢哒嗪-3-酮衍生物除了具有强心作用外,在体外对肿瘤细胞生长还具有抑制作用.     

姜黄素对肝癌的抑制作用实验研究

目的　探讨姜黄素对肝癌的抑制作用。方法　以MTT法观察姜黄素对人肝癌细胞BEL 740 2的抑制作用 ;建立大鼠移植性肝癌模型 ,观察姜黄素对肝癌实体瘤生长的抑制作用。结果　姜黄素具有明显的体外抑制肝癌细胞作用 ,IC50 为 0 .41mg ml;体内抑制肝癌生长作用不明显 ,但可显著延长存活时间     

姜黄素对肝癌的抑制作用实验研究

目的探讨姜黄素对肝癌的抑制作用.方法以MTT法观察姜黄素对人肝癌细胞BEL-7402的抑制作用;建立大鼠移植性肝癌模型,观察姜黄素对肝癌实体瘤生长的抑制作用.结果姜黄素具有明显的体外抑制肝癌细胞作用,IC50为0.41mg/ml;体内抑制肝癌生长作用不明显,但可显著延长存活时间.     

姜黄素与甘草次酸联合用药的体外抗肿瘤作用

目的：研究姜黄素与甘草次酸联合用药的体外抗肿瘤作用。方法：采用MTT法,研究姜黄素、甘草次酸以及姜黄素和甘草次酸联合用药分别对人肝癌细胞株HepG-2、人乳腺癌细胞株MCF-7、人肺癌细胞株A549的细胞增殖抑制率,并计算出相应的IC50值。结果：得到姜黄素、甘草次酸以及姜黄素和甘草次酸联合用药对三种肿瘤细胞株的抑制率IC50值分别为：姜黄素（16.3～19.3μg.mL-1）;甘草次酸（11.6～36.1μg.mL-1）;姜黄素和甘草次酸联合用药（10.5～16.2μg.mL-1）。结论：甘草次酸可以显著加强姜黄素对HepG-2、MCF-7、A549癌细胞增殖的抑制作用,而且两者在癌细胞的增殖抑制方面表现出协同作用。     

Synthesis of Novel Heterocyclic Ring‐Fused 18β‐Glycyrrhetinic Acid Derivatives with Antitumor and Antimetastatic Activity

Glycyrrhetinic acid (GA) is one of the most important triterpenoic acids shows many pharmacological effects, especially antitumor activity. GA triggers apoptosis in various tumor cell lines. However, the antitumor activity of GA is weak, thus the synthesis of new synthetic analogs with enhanced potency is needed. By introducing various five‐member fused heterocyclic rings at C‐2 and C‐3 positions, 18 novel GA derivatives were obtained. These compounds were evaluated for their inhibitory activity against the growth of eight different tumor cell lines using a SRB assay. The most active compound 37 showed IC₅₀ between 5.19 and 11.72 μm , which was about 11‐fold more potent than the lead compound GA. An apoptotic effect of GA and 37 was determined using flow cytometry and trypan blue exclusion assays. We also demonstrated here for the first time that GA and the synthetic derivatives exhibited inhibitory effect on migration of the tested tumor cells, especially 37 which was about 20‐fold more potent than GA on antimetastatic activity.     

Biological evaluation of sulfone derivatives as anti-inflammatory and tumor cells growth inhibitory agents

A variety of sulfone derivatives including three dimethyl arylsulfonyl malonates (1-3), two bis-(arylethenesulfonyl)-vinyl benzenes (4 and 5) and a sulfone triazole (6) were evaluated for their anti-inflammatory as well as tumor cells growth inhibitory activities in vitro. The sulfone derivatives 1, 2, 3 and 6 significantly and dose-dependently inhibited the production of inflammatory mediators such as nitric oxide (NO), and cytokines (tumor necrosis factor (TNF)-alpha and interleukin (IL)-12), in lipopolysaccharide (LPS) and interferon (IFN)-gamma activated murine peritoneal macrophages, without displaying cytotoxicity. The inhibitory mechanism is found through reducing iNOS protein expression. In addition, the derivatives 1-3 significantly arrest mitogen-stimulated spleen cells in G0/G1 stage, whereas compounds 4-6 blocked the same in the G2/M phase. Furthermore, the sulfone derivatives 3 and 6 showed dramatically reduction in the ratio of IFN-gamma to IL-4 production from mitogen-stimulated spleen cells. On the other hand, the novel compounds exhibited interesting cytotoxic activities against a panel of cell lines, particularly, 20 muM of compound 3 showed 50% cytotoxic effect on human hepatoma cell line, but has no effect on normal human peripheral blood mononuclear cells. In conclusion, compound 3 showed interesting anti-inflammatory and tumor cells growth inhibitory functions.     

姜黄素对尤文氏肉瘤RD-ES细胞的诱导凋亡研究

目的 探讨姜黄素对体外培养的人尤文氏肉瘤RD-ES细胞的影响. 方法 体外培养人尤文氏肉瘤RD-ES细胞,姜黄素组加入终浓度分别为1,10,100 mg.mL^-1的姜黄素处理RD-ES细胞,对照组不加姜黄素,24～72 h后观察细胞的形态变化,分别用噻唑蓝(MTT)法、原位末端转移酶标记技术(TUNEL)染色、逆转录 聚合酶链反应(RT-PCR)及图像分析技术检测各组细胞生长、凋亡发生、Bcl-2 基因表达水平的变化. 结果1,10,100 mg.mL^-1姜黄素组细胞生长抑制率分别为(11.8±2.0)%,(56.4±5.0)%,(67.6±6.0)%,24 h半数抑制浓度为10.74 mg.mL^-1;1,10,100 mg.mL^-1姜黄素作用于RD-ES细胞48 h,随着浓度的增强,细胞凋亡率增高;Bcl-2表达减少. 结论 姜黄素可诱导RD-ES细胞凋亡,并与Bcl-2有关.     

Establishment and drug sensitivity evaluation of murine ascites hepatocarcinoma cell line with high lymphatic metastatic potential (Hca-P/L6)

In order to provide a sensitive cell line model for investigating the mechanisms underlying the lymphatic metastasis of tumors and the effect of medicine against cells, a new murine ascites hepatocarcinoma cell line with high lymphatic metastatic potential (Hca-P/L₆) was established and the effect of curcumin on biological behavior of Hca-P/L₆ was observed. Murine ascites hepatocarcinoma cell strain with low lymphatic metastatic potential (Hca-P) was subcutaneously inoculated into the medioventral line of a mouse 615 and the first generation of metastatic tumor cells of inguinal lymph node (Hca-P/L₁) was obtained. Then, Hca-P/L₁ was screened by the route of mouse foot pad subcutaneously → lymph node → scale-up culture in vitro → mouse foot pad subcutaneously for five times consecutively. The sensitivity of two murine ascites hepatocarcinoma cell lines (Hca-P and Hca-P/L₆) and two anchorage-dependent human hepatocarcinoma cell lines (SMC7721 and HepG₂) to curcumin were studied by use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after these cells had been pretreated by curcumin at the concentration of 15–240 μmol/L for 48 h. After pretreatment by curcumin at the maximum non-cytotoxic dose of 15 μmol/L in vitro, the effect of curcumin against cell proliferation of Hca-P and Hca-P/L₆ was observed by inverted microscope, cell growth curve and cell population doubling time; the effects of curcumin on cell cycles of Hca-P/L₆ and Hca-P were studied by flow cytometry (FCM). The results showed Hca-P/L₆ spreading to the lymph nodes at multiple sites in mice was screened from Hca-P. The lymph node metastatic rate was 100%. Curcumin had significant growth inhibiting effect on both murine ascites and human hepatocarcinoma cell lines in a dose-dependent manner (P<0. 05). At concentrations of 30–120 μmol/L, curcumin had more inhibition on murine ascites hepatocarcinoma cell lines than on human anchorage-dependent hepatocarcinoma cell lines. At concentrations of 60–240 μmol/L, curcumin had more inhibition on Hca-P/L₆ with the 50% inhibitory concentration (IC₅₀) of 51.48 μmol/L than on Hca-P with IC₅₀ of 90.87 μmol/L. After pretreatment by curcumin at the maximum non-cytotoxic dose of 15 mol/L for 7 days, the proliferations of Hca-P/L₆ and Hca-P were inhibited (_P<0.05) in a time-dependent manner (P<0.01) and the population doubling time of Hca-P/L₆ and Hca-P was prolonged (P<0.01), and curcumin had more inhibition on Hca-P/L₆ than on Hca-P (P<0.05). After pretreatment by 15 μmol/L curcumin for 48 h, the morphous of Hca-P/L₆ was influenced more seriously than that of Hca-P and the cell cycle was redistributed with Hca-P/L₆ being blocked in the S phase and Hca-P in the S and G₂/M phases. Hca-P/L₆ was validated to be more sensitive to curcumin than Hca-P. Hca-P/L₆ is a novel sensitive cell line model for investigating the mechanisms underlying tumor lymphatic metastasis and the effect of the medicine against cells.     

Newly synthesized curcumin derivatives: crosstalk between chemico-physical properties and biological activity

New curcumin analogues (ester and acid series) were synthesized with the aim to improve the chemical stability in physiological conditions and potential anticancer activity. Cytotoxicity against different tumorigenic cell lines (human ovarian carcinoma cells -2008, A2780, C13*, and A2780/CP, and human colon carcinoma cells HCT116 and LoVo) was tested to evaluate cellular specificity and activity. Physico-chemical properties such as acidity, lipophilicity, kinetic stability, and free radical scavenging activity were investigated to shed light on the structure-activity relationship and provide new attractive candidates for drug development. Most of ester derivatives show IC(50) values lower than curcumin and exhibit selectivity against colon carcinoma cells. Especially they are extremely active after 24 h exposure showing enhanced inhibitory effect on cell viability. The best performances of ester curcuminoids could be ascribed to their high lipophilicity that favors a greater and faster cellular uptake overcoming their apparently higher instability in physiological condition.     

Synthesis and antiproliferative studies of curcumin pyrazole derivatives

A series of curcumin pyrazole derivatives (3a–e) were synthesized. The chemical structures were determined by ¹H and ¹³C NMR spectroscopic techniques and their purity was confirmed by LC–MS and melting point determination. The compounds were screened for anticancer effects on different cancer cell lines by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The analogs demonstrated growth inhibitory effect on MCF-7, HeLa, and K562 cell lines with significant IC₅₀ values. Compound 3b exhibited a high degree of cytotoxicity against cancer cells and minimum growth inhibitory effects against normal cells HEK293T and hence further, cell cycle analysis and mitochondrial membrane potential studies (JC-1 assay) were conducted by utilizing flow cytometry against K562 cells. This compound effectively arrested cell cycle progression at SubG1 phase and cells exhibited decreased membrane potential in a concentration-dependent manner with fluorescence shifting from red to green. Our findings suggest that compound 3b could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in vitro and in vivo investigations.     

白英抗肿瘤活性部位筛选

目的研究白英乙醇提取物及其不同溶剂萃取部分对肿瘤细胞的体外抑制作用,筛选白英抗肿瘤活性部位。方法采用四甲基偶氮唑盐(MTT)比色法。结果白英乙醇提物、乙酸乙酯部位、正丁醇部位对肿瘤细胞均有不同程度的抑制作用;乙酸乙酯部位对A375细胞和Hela细胞的抑制作用较强,IC50 值分别为9 6 9mg·L-1和2 0 90mg·L-1;正丁醇部位对A375细胞和Hela细胞的抑制作用次之,IC50 值分别为31 72mg·L-1和6 4 4 2mg·L-1;水溶性部位对A375细胞和Hela细胞无抑制作用。结论乙酸乙酯部位、正丁醇部位有一定的细胞毒作用,初步确定为白英抗肿瘤活性部位。     

Synthesis and antitumor activity of 1,3-benzodioxole derivatives

A series of 1,3-benzodioxoles (5-19) was synthesized and evaluated for their in vitro antitumor activity against human tumor cell lines. Some derivatives exhibited tumor growth inhibition activity. In particular, 6-(4-aminobenzoyl)-1,3-benzodioxole-5-acetic acid methyl ester 8, the most active compound of the series, possesses a significant growth inhibitory activity on 52 cell lines at concentrations ranging from 10(-7) to 10(-5) M.