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??OBJECTIVE To study the anti-cancer components of Calotropis gigantean L.METHODS The powdered whole plants of C. gigantea were extracted with 95% alcohol. After removal of the solvent, the residue was extracted with petroleum ether and chloroform, and the compounds in the chloroform extract were isolated and purified by different column chromatograghies carried out on silica gel, RP-18, MCI, and Sephadex LH-20 and their structures were elucidated by spectral data. RESULTS Thirteen compounds were isolated and their structures were characterized as gofruside(1), uzarigenin(2), arjunolic acid(3), 3??-(1??-hydroxyethyl)-7-hydroxy-1-isobenzofuranone(4), daucosterol(5), syringaresinol(6),12-O-benzoyl-deacylmetaplexigenin(7), 3-hydroxy-4-methoxybenzoic acid(8), oleanolic acid(9),??-sitosterol(10), methyl 1-naphthaleneacetate(11), butylparaben(12),??-D-oleandropyranoside(13), and compounds 2-4,6-9, and 11-13 were isolated from this plant for the first time. Compounds 1 and 2 showed cytotoxicity against HLE, K562, RPMI8226, MCF7, MDA, and WM9 cell lines, with K562 and RPMI8226 being the most sensitive cells.CONCLUSION Compounds 1 and 2 are premilinarily judged as the anti-cancer components in C. gigantean.     

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??OBJECTIVE To design and synthesize series of quercetin derivatives by introducing allyl or prenyl groups and investigate their antitumor activities in vitro.METHODS Compounds 2, 3, 4, 5, 6, 7 and 8 were synthesized with quercetin as starting material through the etherification reaction.The antitumor activities were evaluated by MTT assay against human lung cells (A549), human breast cancer cells (MDA-MB-231), and human hepatoma cells (HepG2).RESULTS Two allyl-substituted and five prenyl-substituted quercetin derivatives were synthesized. Compounds 4, 5, 6, 7, and 8 were new compounds, and their structures were characterized by ¹H-NMR and ¹³C-NMR. Compounds 6 and 7 exhibited observable anti-proliferative activity. Compound 6 inhibited the growth of A549, MDA-MB-231, and HepG2 cells with IC₅₀ values of 15.23, 16.56, and 12.32 ??mol??L^-1, respectively.Compound 7 restrained the growth of A549 and MDA-MB-231 cells with IC₅₀ values of 8.92 and 2.90 ??mol??L^-1, respectively. CONCLUSION Compounds 6 and 7 synthesized by introducing prenyl groups into quercetin have significant anti-tumor activities, which are worth of further research.     

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??OBJECTIVE To study the chemical constituents of Noni enzyme (Morinda citrifolia L.) and their antitumor activities. METHODS Compounds were isolated by various chromatographic techniques, including silica gel, TLC, sephadex LH-20, and semi-preparative HPLC, and their structures were identified by their physicochemical properties and ¹H-NMR and ¹³C-NMR data. The in vitro antitumor activities of the isolated compounds were studied by MTT method. RESULTS Sixteen compounds were isolated from Noni enzyme. They were xylogranatinin(1), pelargonic acid(2), 1,5,15-tri-O-methylmorindol(3), sesquipinsapol B(4), (+)-syringaresinol(5), pinonesinol(6), 3-methylhexahydropyrrolopyrazine-1,4-dione(7), (2S)-3??-hydroxybutan-2-yl-2-hydroxypropanoate (8), 3-(sec-butyl)-6-methylpiperazine-2,5-dione(9), cyclo-(L-Pro-L-Leu)(10), gentisic acid(11), vomifoliol(12), scopoletin(13), 3-(2-hydroxy-4,5-dimethoxyphenyl) propanoic acid(14), medioresinol(15), hydroxychavicol(16). CONCLUSION Compounds 1-10, 12 and 14-16 are isolated from Noni enzyme for the first time. Compound 10 displays the stronger cytotoxicity against HepG2 and HeLa cells with an IC₅₀ value of 23.73, 16.55 ??g??mL^-1. Compound 5 had a certain inhibitory activity against HeLa cells with an IC₅₀ value of 47.12 ??g??mL^-1.     

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??OBJECTIVE To prepare luteolin-loaded Solutol hs15/Poloxamer188 mixed micelles, evaluate their pharmaceutical property and study their anti-tumor activity. METHODS The luteolin-loaded mixed micelles were prepared by thin-film hydration method. The particle size was measured by laser granulometry, and the morphology was observed under transmission electron microscope (TEM). The in vitro release behavior was determined by the dialysis method. Cell toxicity and uptake assays were employed to evaluate the anti-tumor activity. The targeting effect was studied by fluorescence labeling. RESULTS The prepared luteolin-loaded mixed micelles showed spherical and regular shape with an average particle size of 66.43 nm and its entrapment efficiency was more than 80%. The 12 h-accumulated release ratio in vitro was up to 97.42%. The cytotoxicity of luteolin-loaded mixed micelles on human lung adenocarcinoma cell line A549 was significantly stronger than that of free luteolin and the uptake rate was improved. After injecting DiR-loaded mixed micelles into nude mouse, the drug begun to accumulate in tumors after 2 h and reached the highest concentration at 6 h which was significantly higher than that in other tissues. There remained strong drug distribution in the tumors after 12 h. CONCLUSION The Solutol hs15/ Poloxamer188 mixed micelles have small particle size and high entrapment efficiency and can enhance cell toxicity and uptake with certain passive targeting effect. It is a promising delivery system for anti-tumor drug.     

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??OBJECTIVE To study the chemical constituents of the leaves of Magnolia grandiflora Linn and their antitumor activities. METHODS The constituents were isolated and purified by various chromatographic METHODS, including column chromatographies on silica gel, Sephadex LH-20, as well as recrystallization. Their structures were identified by analysis of physical and spectral data and confirmed by comparison of their spectral data with the reported values in the literature or those of authentic samples. The antiproliferative activities of the purified compounds were evaluated by MTT assay. RESULTS Twelve compounds were isolated and identified as parthenolide(1), ergosterol peroxide(2), N-formyl-annonain(Z)(3_Z), N-formyl-annonain(E)(3_E), vitamin E quinone(4), ??-sitosterol(5), 11,13-dehydrocompressanolide(6), scoparone(7), liriodenine(8), aurantiamide acetate(9), michelenollide(10), and 2,6,2??,6??-tetramethoxy-4,4??-bis(2,3-epoxy-1-hydroxypropyl)biphenyl(11). CONCLUSION Compounds 2, 3_Z, 3_E, and 4 are isolated from this plant for the first time. Compounds 9 and 11 are isolated from the plants in Magnoli Linn for the first time.     

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??OBJECTIVE To design and synthesize 4-phenoxy-6,7-disubstituted quinolines possessing thiazolinone scaffolds and investigate their in vitro antitumor activities. METHODS Taking the c-Met kinase inhibitor cabozantinib as lead compound and based on the obtained SARs, combination principles and local modification, target compounds were prepared by nucleophilic substitution, nitration, reduction and condensation, etc. The c-Met inhibition and in vitro antitumor activities were evaluated by HTRF and MTT methods, respectively. The cytotoxicity against cancer cells was evaluated by real-time dynamic living cell imaging. RESULTS Seventeen novel compounds were obtained, and their structures were confirmed by ¹H-NMR, ¹³C-NMR and HRMS. In vitro bioassay indicated that all the compounds showed inhibitory activities against A549, HepG2 and MDA-MB-231 cell lines as well as c-Met kinase. Compound m2 exhibited potent cytotoxicity with IC₅₀ values of 2.45, 4.01, and 1.05 ??mol??L^-1, respectively. CONCLUSION The series of compounds show preferable antitumor activities, which are worthy of further study.     

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??OBJECTIVE To investigate the chemical constituents in chloroform extraction of Tetrastigmatis hemsleyani diels et. Gilg and their antitumor activities. METHODS Various chromatography techniques such as column chromatography on silica gel, Sephadex LH-20 and preparative TLC were used to isolate and purify the compounds. Their structures were identified by¹H-NMR,¹³C-NMR and MS. Their antitumor activities was tested by MTT method. Moreover, the other compounds of chloroform extraction were detected by GC-MS. RESULTS Six compounds were isolated by classic chromatography and identified as ??-sitosterol(1), 4-hydroxy-3-methoxybenzaldehyde(2), oleanolic acid (3), 5-hydroxymethyl furfural(4), azelaic acid(5), vanillic acid(6). Twenty-two compounds were identified by GC-MS. CONCLUSION Compounds 2-6 are isolated from this plant for the first time. Compounds 1 and 3 shows strong cytotoxic activities against Hela229 with IC₅₀ values of 40.78, 25.69 ??g??mL^-1, respectively. Compound 3 also showed strong cytotoxic activities against with IC₅₀ values of 69.87 ??g??mL^-1. The result proved that antitumor activity of chloroform extraction of Tetrastigmatis hemsleyani diels et. Gilg is due to the contribution of multi-components.
     

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??OBJECTIVE To explore the synthesis of novel phenylalanine dipeptide derivatives and their inhibitory effects on tumor cells. METHODS Starting from L-phenylalanine or L-tyrosine, a series of derivatives were synthesized by reaction with chloroacetyl chloride, followed by condensation with L-phenylalaninol or L-phenylalanine methyl ester hydrochloride and nucleophilic substitution reaction with differently substituted phenol.The cell proliferation inhibiting activities of the derivatives were evaluated by thiazolyl blue tetrazolium bromide(MTT)method.RESULTS Some of the target compounds showed certain inhibitory effect for leukemia cell lines K562 and HEL in vitro.Furthermore, the derivatives 3f and 3q had preferably inhibitory effect on K562 cell line prostate cancer PC3 cells in vitro.CONCLUSION Phenylalanine dipeptide derivatives possess good effect on the leukemia and prostate cancer cells and are worth of further research.     

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??OBJECTIVE To further design and synthesize Desmosdumotin-C(Des-C) derivatives and investigate their antitumor activities. METHODS QSAR study using the CoMFA method was performed on a set of reported Des-C derivatives to facilitate the elucidation of their SAR and discovery of new potent Des-C derivatives. Flow cytometry was used to investigate antitumor activity. RESULTS The established model showed good predictive ability and aid in the design of potent Des-C derivatives. An efficient three-step synthetic strategy toward Des-C derivatives was developed and applied to synthesize 10 new derivatives which showed superior antitumor activities against A549 and HL60 cells in vitro. CONCLUSION The structural modification of Des-C would significantly increase the antitumor activity. It is preliminarily confirmed that the derivatives are potent antitumor agents with apoptosis-inducing ability, which provides the basis for the further study.     

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??OBJECTIVE To characterize the population pharmacokinetics of isoniazid in Chinese tuberculosis patients. METHODS A total of 321 serum samples were obtained from 201 patients receiving oral doses of isoniazid. The effects of 16 covariates including demographics and blood tests to isoniazid??s pharmacokinetics were evaluated. Data analysis was performed using non-linear mixed effects modeling (NONMEM). Prediction-corrected visual prediction check was performed for model evaluation. RESULTS A two-compartment model with first-order absorption and linear elimination can well fit the isoniazid concentration-time data. A ??MIXTURE?? model was used to separate the subpopulation of ??subgroup A?? and ??subgroup B??. Typical clearance of the two subpopulations were 82.7 and 19.3 L??h^-1, respectively. CONCLUSION Model validation shows the final model is reliable, which could be used for individualized treatment.     

蘘荷提取物抗氧化能力及抑菌作用

目的:以新鲜蘘荷Zingiber mioga花蕾为原料,探讨蘘荷花蕾不同提取部位的抗氧化作用,并筛选其有效抑菌部位。方法:蘘荷花蕾用甲醇提取浓缩,依次萃取得到石油醚、二氯甲烷、乙酸乙酯、正丁醇和水等5个萃取部位后,采用1,1-二苯基-2-三硝基苯肼(DPPH)自由基清除模型评价不同萃取部位抗氧化能力,用打孔扩散法考察萃取部位对大肠埃希菌、沙门氏菌、金黄色葡萄球菌和铜绿假单胞菌的体外抑菌活性。结果:加热回流法提取蘘荷花蕾,提取率为3.1%,其中乙酸乙酯部位DPPH自由基清除能力最高,半数抑制率(IC50)达到(26.22±1.12)mg·L-1,对铜绿假单胞菌的抑菌圈达到(10±1)mm,石油醚部位抑菌活性最高,对金黄色葡萄球菌的最低抑菌浓度(MIC)最低,达到25.0 mg·L-1。结论:蘘荷花蕾各部位均有一定的抗氧化能力,综合抑菌效果比较石油醚部位二氯甲烷部位乙酸乙酯部位甲醇提取物,为蘘荷花蕾抗氧化产品、抑菌剂的开发利用提供理论基础。     

响应面法优化天仙果总黄酮提取工艺及抗氧化活性研究

目的 优化天仙果总黄酮提取工艺,并测定其抗氧化活性。方法 通过响应面优化建立数学模型,考察乙醇体积分数、料液比、提取时间、提取次数4个因素,得到天仙果总黄酮最优提取条件。考察天仙果抗氧化活性,进行1,1-二苯基-2-三硝基苯肼（DPPH）法、2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐（ABTS）法、羟自由基清除能力的测定。结果 天仙果总黄酮最佳提取工艺为乙醇体积分数60%、料液比1∶23、提取时间18 min、提取1次,在此条件下,提取率为16.25 mg·g^–1,天仙果总黄酮对DPPH、ABTS、羟自由基清除率分别为92.84%、89.34%、69.73%。结论 优化后的提取工艺可操作性强、稳定可靠,天仙果抗氧化活性好。     

木蝴蝶总黄酮的抗氧化活性

目的:研究木蝴蝶总黄酮的抗氧化活性。方法:采用二苯代苦味酰基苯肼(DPPH)法、水杨酸法和邻苯三酚自氧化法来考察其抗氧化活性,并与Vc做比较。结果:在试验浓度内,木蝴蝶总黄酮对二苯代苦味酰基苯肼自由基(DPPH.)、羟自由基(.OH)和超氧阴离子自由基(O2-.)均有较好的清除作用,其EC50分别为19.73,231.70,318.93 mg·L-1,在9.52～57.12 mg·L-1,其对DPPH.的清除率高于VC。结论:木蝴蝶总黄酮有良好的抗氧化活性,具有进一步开发利用的价值。     

石榴叶总黄酮的提取工艺及抗氧化活性考察

目的:优化石榴叶总黄酮的提取工艺,并对其体外抗氧化活性进行评价,为该部位的开发提供参考。方法:在单因素试验基础上,选择乙醇体积分数、料液比、超声功率、超声时间为考察因素,石榴叶总黄酮提取率为评价指标,根据BoxBehnken设计原理,采用响应面法优化石榴叶总黄酮的提取工艺。通过DPPH和·OH的清除能力考察石榴叶总黄酮的体外抗氧化活性。结果:石榴叶总黄酮最佳超声提取工艺为乙醇体积分数59.8%,料液比1∶16.3,超声功率221 W,提取时间33.45 min;石榴叶总黄酮提取率0.433%,与理论值偏差很小。当样品质量浓度为0.6~1.0 g·L-1时,对DPPH和·OH清除率较高,与维生素C接近。结论:优选的提取工艺稳定可行、提取率高,石榴叶总黄酮抗氧化性能较强,为该部位的工业化生产提供参考。     

响应面法优化冰糖草总黄酮提取工艺及抗氧化活性分析

目的:研究冰糖草总黄酮的提取工艺及抗氧化活性.方法:以总黄酮提取量为指标,利用Box Behnken设计三因素三水平进行响应面试验,确定最佳提取工艺;采用清除1,1-二苯基-2-三硝基苯肼(DPPH)自由基和测定总还原能力的方法评价总黄酮的抗氧化活性.结果:最佳提取工艺为乙醇体积分数72％,液料比32:1,超声温度55...     

超声辅助碱溶酸沉法提取铁苋菜总黄酮的工艺优选

目的: 优选超声辅助碱溶酸沉法提取铁苋菜总黄酮的工艺条件。 方法: 以芦丁为对照成分,采用紫外-可见分光光度法测定铁苋菜总黄酮含量。以总黄酮得率为指标,在单因素试验基础上,通过正交试验考察料液比、碱性提取液pH、温度、酸沉pH和时间对铁苋菜总黄酮提取工艺的影响。 结果: 铁苋菜总黄酮最佳提取工艺为料液比1:20,碱提液pH 11,温度60 ℃,酸沉pH 2.5,超声时间90 min,提取数1次;铁苋菜总黄酮提取量24.11 mg·g^-1,提取率达87.76%。 结论: 优选的提取工艺稳定可行、提取率高,为铁苋菜资源的开发利用提供实验依据。     

大苞雪莲总黄酮体外抗氧化活性

目的:研究大苞雪莲总黄酮体外自由基清除能力及抗氧化活性。方法:采用体外清除1,1-二苯基-2-三硝基苯肼自由基(DPPH·),2,2-联氮基-双-(3-乙基苯并噻唑啉-6-磺酸)二氨盐阳离子自由基(ABTS+·),超氧阴离子(O-2·),羟基自由基(·OH),一氧化氮(NO),以及测定金属螯合能力、还原力、总抗氧化能力共8种方法对大苞雪莲总黄酮的自由基清除能力及抗氧化活性进行了评价。每组实验平行3次。结果:大苞雪莲总黄酮在一定浓度下能够有效地清除DPPH·,ABTS+·,O-2·,·OH,NO,对DPPH·,ABTS+·,·OH,NO的半数清除质量浓度分别为52.52,71.71,60.38,203.95 mg·L-1,对超氧阴离子的半数清除质量浓度为271.06 mg·L-1,小于维生素C(VC,380.10 mg·L-1),半数金属螯合质量浓度为184.52 mg·L-1,并且具有一定的还原力和总抗氧化能力。结论:大苞雪莲总黄酮具有较强的体外自由基清除能力及抗氧化活性,是一种具有较高研究价值和潜力的天然抗氧化物质。     

新疆4种山楂果实中总黄酮的纯化与抗氧化活性考察

目的:优选大孔树脂纯化4种新疆山楂果实总黄酮的工艺条件,评价其抗氧化活性。方法:以总黄酮纯度为评价指标,比较13种大孔树脂对4种山楂果实总黄酮的吸附分离效果,考察上样流速、洗脱剂浓度对4种山楂总黄酮大孔树脂纯化工艺的影响。以清除2,2'-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐(ABTS)和二苯代苦味酰基(DPPH)自由基的方法测定样品的抗氧化活性,利用HPLC测定样品芦丁和金丝桃苷的含量,流动相乙睛-0.4%甲酸溶液(16:84),检测波长360 nm。结果:选择HPD722型大孔树脂纯化总黄酮,最佳纯化工艺条件为上样流速0.84 mL·min^-1,总黄酮经树脂充分吸附后,加40%乙醇动态洗脱。经HPD722型大孔吸附树脂纯化后,4种山楂的总黄酮、芦丁、金丝桃苷质量分数和抗氧化活性分别提高了1.9~3.3,2.4~5.1,2.6~3.7,2.0~4.6倍。结论:HPD722型大孔树脂可有效地对4种新疆山楂果实总黄酮进行富集纯化,为这4种药材资源的充分利用提供参考。     

神农香菊茎叶总黄酮与总酚的提取纯化和抗氧化活性研究＊

目的 提高神农香菊茎叶总黄酮与总酚的产率和纯度并探究其抗氧化机制。方法 采用正交试验设计，优化神农香菊茎叶总黄酮和总酚的提取参数。使用大孔树脂吸附技术，对提取物中总黄酮和总酚进行纯化。通过UPLC-MS/MS分析纯化前后提取物中黄酮和酚酸类成分的含量变化。采用1，1-二苯基-2-苦肼基（DPPH）清除试验和分子对接评价提取物的抗氧化潜力。结果 最佳提取工艺为：料液比1：5 g·mL^-1，乙醇浓度70%，提取时间60 min。最佳纯化条件为：上样浓度0.12 g·mL^-1，上样体积3 BV，上样流速3.0 BV/h，洗脱溶剂80%乙醇，洗脱流速4.5 BV/h，洗脱体积4 BV。与纯化前相比，纯化后提取物中总黄酮和总酚纯度分别提高了2.85倍和4.03倍。UPLC-MS/MS分析证实，纯化后部分黄酮和酚类物质含量显著增加。此外，神农香菊茎叶提取物显示出较强的DPPH自由基清除活性，其黄酮成分与黄嘌呤氧化酶具有较强结合能力。结论 本文对神农香菊茎叶总黄酮与总酚的富集和纯化具有重要指导意义，并表明了其潜在抗氧化价值。     

冷水花总黄酮的提取工艺优选及抗氧化活性考察

目的:测定不同产地冷水花中总黄酮的含量并评价其抗氧化活性。方法:在单因素试验基础上,以总黄酮提取量为指标,选择料液比、提取温度、提取时间为考察因素,采用响应面法优化冷水花总黄酮的提取工艺,测定不同产地冷水花样品中总黄酮的含量并考察其抗氧化活性。结果:最佳提取工艺为料液比1∶19,提取温度71℃,提取时间126 min。冷水花总黄酮提取量7.08 mg·g-1;不同产地样品中总黄酮质量分数4.35~7.10 mg·g-1,具有明显的地域差异性。冷水花总黄酮对1,1-二苯基苦基苯肼和2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐自由基的清除能力与维生素C相当。结论:不同产地冷水花中总黄酮具有较好的抗氧化能力,且该能力与总黄酮含量具有明显量效关系。