多羟基甾醇的合成及其结构与抗扣瘤细胞活性关系研究

报道了６个具有类似结构的多羟基甾醇的合成和它们的抗肿瘤细胞活性。发现此类化合物的细胞毒性与其分子中双键存在与否有着密切关系。当甾核或支链中双键被饱和时，其细胞毒性均明显降低。甾醇（５）和（８）对胃癌（ＭＧＣ）、宫颈癌（ＨＥＬＡ）细胞的生长具有一定的抑制作用。     

β-谷甾醇、豆甾醇与DPPC相互作用的单分子膜研究

植物甾醇对生物膜具有重要的调节作用,甾醇尾部的饱和程度对生物膜性质的影响一直是个热点问题.通过LB技术和原子力显微镜分别研究了尾部是单键的β-谷甾醇(β-sito)和尾部是双键的豆甾醇(stig)与二棕榈酰磷脂酰胆碱(DPPC)的相互作用,深入分析了β-谷甾醇、豆甾醇对DPPC单分子膜液态扩张-液态聚集(LE-LC)相变过程的影响.实验结果表明:β-谷甾醇、豆甾醇添加到DPPC单分子膜中,膜的压缩性以及分子的排列都发生了较大变化.当植物甾醇含量Xsterols=0.8时,β-谷甾醇、豆甾醇与DPPC相互作用具有相同的规律,过量分子面积和过量吉布斯自由能均为负值,说明分子间的吸引力比排斥力更强;在低浓度下,Xsterols=0.2,0.4时,两种系统的过量分子面积和过量吉布斯自由能呈现出明显的区别,尾部是单键的β-谷甾醇和DPPC混合单分子膜的排斥力更强烈,而尾部是双键的豆甾醇和DPPC混合单分子膜的吸引力更强烈,说明尾部是双键的豆甾醇比尾部是单键的β-谷甾醇更容易和DPPC发生凝聚,AFM数据进一步证实了这些结果.     

中国南海软珊瑚Nephthea Sinulata中的一个新甾醇

海洋软珊瑚中多羟基甾醇已有不少报道.本文报道从我国西沙群岛采集的软珊瑚Nephthea sinulata的乙醇抽提物中分离到的一个新甾醇1的结构鉴定. 1由质谱和元素分析确定其分子式为C_(30)H_(48)O_4,400MHz ~1H NMR示有末端双键(4.63、4.69ppm各一个质子,宽单峰),1个三取代的双键(5.55ppm,1H,d,J=2Hz).δ0.73ppm处单峰(3个质子)归于C-18角甲基,甾醇中常见的C-19角甲基信号δ1.00～1.10(3H,s)消失,代替出现的是一个2组二重峰(3.63、3.66ppm,2H,ABq,J=12Hz).这归属于C-     

两种新的多羟基甾醇化合物分离与结构鉴定

采用现代分离手段,从采自中国南海硇洲岛的软珊瑚Chromonephthea sp.中分离纯化得到两种甾醇化合物,经过MS,IR,1H NMR,13C NMR(DEPT),HSQC,HMBC和NOE等光谱技术鉴定它们的结构为:24-甲基胆甾-5-烯-3β,12β,16β,20-四醇(1)和24-乙基胆甾-5-烯-3β,12β,16β,20-四醇(2),这两个化合物均为新化合物.肿瘤活性实验表明两种甾醇化合物显示微弱的细胞毒性.     

具有细胞毒性的两种四羟基甾醇化合物的分离与结构

报道南海湛江硇洲岛软珊瑚Dendronephthya sp.中两种具有细胞毒性的四羟基甾醇化合物:23-降-24-亚甲基-麦角甾-3β,5α,6β,7β-四醇(1)和24-亚甲基-麦角甾-3β,6β,9α,19β-四醇(2),其结构通过波谱和化学方法确定,其中化合物1为新化合物,化合物2首次从该属珊瑚中获得.化合物1对肿瘤细胞BEL-7402,MCG,MCF,LOVO和HepG-2具有抑制作用,其IC50值分别为32.2,20.5,2.0,5.5和18.6μg/mL;化合物2对肿瘤细胞MCG和LOVO作用的IC50值分别为22.0和和13.8μg/mL.     

SiO_2含量对含联苯结构牙科复合树脂性能影响的研究

通过四甲基联苯二酚型环氧树脂(TMBP)与丙烯酸进行开环酯化反应制备出四甲基联苯二酚型环氧丙烯酸酯(TMBPEA),研究无机填料硅烷化纳米/微米混合SiO_2的添加量对该复合树脂固化体系双键转化率、聚合收缩率和细胞毒性的影响.结果表明:随着树脂体系中SiO_2添加量的增加,复合树脂的双键转化率和聚合收缩率呈降低趋势,并且材料的细胞毒性不受SiO_2添加量的影响.其中, SiO_2质量分数为60%的TMBPEA复合树脂双键转化率和聚合收缩均最低,分别为(48.75±2.30)%和(1.21±0.46)%.各组复合树脂的细胞毒性等级均为≤1级.     

两个新的化合物线四肽和单羟基甾醇的分离与结构鉴定

采用现代分离手段,从采自中国南海硇洲岛的白穗软珊瑚Nephthea sp.中分离纯化得到两个新的化合物分别为线四肽化合物和单羟基甾醇,经过MS,1H NMR,13C NMR(DEPT),HSQC,HMBC和NOE等光谱技术鉴定它们的结构为:亮氨酰-N-甲基亮氨酰-亮氨酰-N-甲基亮氨酸(1)和(20S,22R)-孕甾-1,4-二烯-22-乙酰基-3-酮(2),这两个化合物均为新化合物.肿瘤活性实验表明两个新的化合物显示微弱的细胞毒性.     

19—羟基甾醇Nephalsterol—B的结构研究

前文报道了从西沙群岛采集的软珊瑚Nephthea albida和南沙群岛采集的软珊瑚Nephthea tixiexae verseveldt分离到一种罕见的含19-羟基的四羟基甾醇Nephalsterol A(1).本文报道从N.tixiexae verseveldt分离到的另一种19-羟基甾醇Nephalsterol-B的结构测定. Nephalstereol B(2)为无色针状结晶,m.p.159～161℃(乙酸乙酯);160～162℃(丙酮),[α]_D~(27)+25°(C 0.100,甲醇),2的~(13)C NMR及其DEPT谱表明分子中含有4个CH_3,11个     

分光光度法测定火龙果茎中的植物甾醇

建立了Liebennann-Burchard显色法测定火龙果茎中植物甾醇含量的方法.以豆甾醇为标样,植物甾醇含量在0.02～0.20 mg/mL范围内,服从比耳定律,回归方程为A=4.489σ+0.0339,相关系数R=0.9997,方法的回收率为98.7%,相对标准偏差(RSD)为3.8%(n=5).     

新甾醇—绿柱虫甾醇A的结构测定

从中国南海采集的绿柱虫软珊瑚中分离到一种具有环丙烷结构的支链的新甾醇——绿柱虫甾醇A(clavisterol A.).通过各种波谱分析,确定了其结构.     

Structure and Activity of a New Sapogenin from Chlorophytum laxum R. Br.

A new steroidal sapogenin named 25-R-spirosta-3,5-dien-12β-ol(1) was isolated from the dried roots of Chlorophytum laxum R. Br. along with five known compounds, namely, diosgenin(2), stigmasterol(3), β-sitosterols(4), estigmasterol-3-O-β-D-glicopyranoside(5) and 3-O-β-authemisol(6). The structure of compound 1 was elucidated by the analysis of IR, HRESI-MS, 1D and 2D NMR spectral data. Compounds 2-5 were isolated from Chlorophytum laxum R. Br. In addition, all the compounds were evaluated for cytotoxicity on the human nasopharyngeal carcinoma cancer cell line 5-8F. Among them, the newly identified 25-R-spirosta-3,5-dien-12β-ol(1) and diosgenin(2) exhibited high cytotoxicity on 5-8F cells, with IC₅₀ values of 24.8 and 41.9 μmol/L, respectively.     

Facile preparation and characterization of novel oleanane-type triterpene functionalized β-cyclodextrin conjugates

Four water-soluble β-CD-pentacyclic triterpene conjugates were synthesized via ester and amide linkages. All the conjugates showed lower hydrophobicity (AlogP) than their parent.     

Synthesis and Biological Evaluation of S-, O- and Se-Containing Dispirooxindoles

A series of novel S-, O- and Se-containing dispirooxindole derivatives has been synthesized using 1,3-dipolar cycloaddition reaction of azomethine ylide generated from isatines and sarcosine at the double C=C bond of 5-indolidene-2-chalcogen-imidazolones (chalcogen was oxygen, sulfur or selenium). The cytotoxicity of these dispiro derivatives was evaluated in vitro using different tumor cell lines. Several molecules have demonstrated a considerable cytotoxicity against the panel and showed good selectivity towards colorectal carcinoma HCT116 p53^+/+ over HCT116 p53^−/− cells. In particular, good results have been obtained for LNCaP prostate cell line. The performed in silico study has revealed MDM2/p53 interaction as one of the possible targets for the synthesized molecules. However, in contrast to selectivity revealed during the cell-based evaluation and the results obtained in computational study, no significant p53 activation using a reporter construction in p53wt A549 cell line was observed in a relevant concentration range.     

聚(L-天冬氨酸)衍生物-顺铂结合物的制备及体外细胞毒性研究

通过α,β-聚(L-天冬氨酸)及其衍生物α,β,L-天冬氨酸和[α,β,L-(N-羟乙基)天冬酰胺]共聚物,[α,β,L-(N-羟乙基)天冬酰胺]和[α,β,L-(N-丁二酸基)天冬酰胺]共聚物为载体,与顺式二氯二氨合铂(Ⅱ)结合,合成了相应高分子-顺铂结合物.研究结果表明,在中性pH值络合最有效,聚合物-顺铂结合物的体外细胞毒性随结合物浓度增大而增大,但均小于同浓度顺铂毒性.     

Microcionamides A and B, bioactive peptides from the philippine sponge Clathria (Thalysias) abietina

Microcionamides A (1) and B (2) have been isolated from the Philippine marine sponge Clathria (Thalysias) abietina. These new linear peptides are cyclized via a cystine moiety and have their C-terminus blocked by a 2-phenylethylenamine group. Their total structures, including absolute stereochemistry, were determined by a combination of spectral and chemical methods. Compound 1 was shown to slowly isomerize about the C-36/C-37 double bond when stored in DMSO. Microcionamides A (1) and B (2) exhibited significant cytotoxicity against the human breast tumor cells lines MCF-7 and SKBR-3 and displayed inhibitory activity against Mycobacterium tuberculosis H(37)Ra.     

Inhibitory effect of 2-(E-2-alkenoylamino)ethyl alkyl sulfides on gastric ulceration in rats. II. Structure and activity relationships of 2-(E-n or Z-n-Decenoylamino)ethyl alkyl sulfides

The analogues of 2-(E-n or Z-n-decenoylamino)ethyl carbamoylmethyl sulfide, including the modifications of sulfide portion, double bond in decenoyl chain and alkyl sulfide moiety, were synthesized and their inhibitory effects on stress-induced ulceration in rats were compared. Replacing the sulfura atom by methylene group or oxygen atom reduced the effect of potency. Saturation of the double bond in the decenoyl chain tended to reduce the anti-ulcerogenic activity in rats. There was no relationship between the position of double bond in decenoyl chain and the pharmacological activity. On the other hand, compounds with E-configuration showed stronger anti-ulcer activity than the corresponding Z-type of compounds. Among 9 kinds of S substituted alkyl groups for carbamoylmethyl, 2-(E-2-decenoylamino)ethyl 2-cyclohexylethyl sulfide showed the most potent anti-ulcerogenic activity in rats and also showed the lowest acute toxicity in mice.     

Microbial transformation of diosgenin by Syncephalastrum racemosum (Cohn) Schroeter

<正>Microbial transformation of diosgenin(1) by Syncephalastrum racemosum yielded five new polar metabolites,which wereidentified as(25R)-spirost-5-en-3β,7α,9α-triol-12-one(2),(25R)-spirost-5-en-3β,9α,12α-triol-7-one(3),(25R)-spirost-5-en-3β,9α-diol-7,12-dione(4),(25R)-spirost-4-en-9α,12β,14α-triol-3-one(5),and(25S)-spirost-4-en-9α,14α,25β-triol-3-one(6).Compounds 1-6 exhibited moderate cytotoxicity against K562 cells and among them compounds 2,3,and 6 were more potentthan the parent compound 1.     

The correlation between molecular weight and antitumor activity of galactosaminoglycan (CO-N) from Cordyceps ophioglossoides

A galactosaminoglycan (CO-N) obtained by ultrasonication from a protein-bound polysaccharide SN-C, which was isolated from Cordyceps ophioglossoides culture, has a direct cytotoxicity against tumor cells (Ohmori et al., Chem. Pharm. Bull., 37, 1019 (1989). High performance liquid chromatographic analysis revealed that CO-N shows a broad molecular weight distribution with an average molecular weight of 33000. A potent antitumor activity of CO-N was observed in the higher-molecular-weight fraction on gel filtration, and the low-molecular-weight fraction below 6600 showed a weak activity. However, the depolymerized CO-N (ca. 5500) obtained by further ultrasonication of the original CO-N still retained the antitumor activity of CO-N against Ehrlich ascitic carcinoma or MM46 solid mammary carcinoma.     

Synthesis and antitumor activity of some new pyrazolo[1,5-a] pyrimidines

New series of pyrazolo[1,5-a]pyrimidine derivatives 7a-i, 11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines, namely colorectal carcinoma (HCT116), prostate adenocarcinoma (PC-3) and liver carcinoma (HepG-2) using MTT cytotoxicity assay at 100 μg/mL. Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells. Whereas, compounds 7d and 11a showed better antitumor activity than the rest of the compounds against both cell lines. A structure-activity relationship (SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data (MS, IR, ¹H NMR and ¹³C NMR) and elemental analysis.     

Amino acid derivatives,part 3: New peptide and glycopeptide derivatives conjugated naphthalene. Synthesis,antitumor, anti‐HIV,and BVDV evaluation

A series of peptide derivatives conjugated naphthalene residue 11–25 , the glycoside 27 as well as the 7‐glycoside 30 , and the 2‐(2‐hydroxy‐3‐(N‐benzyl‐N‐isopropylamino)propoxy)naphthalene bearing methionine 31 were synthesized. The new compounds were evaluated in vitro for cytotoxicity against HIV‐1 and bovine viral diarrhea virus (BVDV), where 31 showed remarkable activity against HIV‐1. The cytotoxicity, in vitro, of 11–25 and 27 was assayed against a panel of tumor cell lines consisting of CD4 human T‐cells containing an integrated T‐leukemia virus type 1 (HTLV‐1), CD4 human acute T‐lympho‐ blastic leukemia, splenic B‐lympho‐blastoid cells, acute B‐lymphoblastic leukemia, mela‐noma, breast adenocarcinoma, lung squamous carcinoma, hepatocellular carcinoma, prostate carcinoma, foreskin fibroblasts, and lung fibroblasts. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:576–585, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20149