Studies on the synthesis andin vitro antitumor activity of the isoquinolone derivatives

3-Arylisoquinolin-1(2H)-ones (2) are possible bioisosteres of the 5-[4'-(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-a]iso quinoline (1) which is in clinical evaluation for the treatment of cancer. Structure-activity relationship studies of 3-arylisoquinolin-1(2H)-ones (2) led to the synthesis of 3-arylquinolin-2(1H)-ones (3). A number of 3-phenyl substituted quinolin-2(1H)-ones were synthesized and tested for their in vitro antitumor activity against four different human tumor cell lines and 3-phenyl-N-benzyl-3,4-dihydroquinolin-2(1H)-one (12) showed the most potent activity.     

Synthesis andin vitro antitumor activity of 2-alkyl, 2-aryl, and 2-piperazinyl benzimidazole-4,7-dione derivatives

A series of 2-alkyl, 2-aryl, and 2-piperazinyl benzimidazole-4,7-dione derivatives (7a-h) and 16m-o) were prepared, and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia cell line P388, and human gastric carcinoma cell lines SNU-1 and SNU-16). These compounds showed potent cytotoxicity against all of three cell lines tested, and especially SNU-16 was sensitive to them. 2-Aryl (7g,h) and 2-piperazinyl benzimidazole-4,7-dione derivative (16 m) were more potent than mitomycin C against P388 and SNU-16. Among benzimidazole-4,7-dione derivatives with alkyl group at position 2, 7a had the most potent cytotoxicity against all of the cell lines tested.     

积雪草酸衍生物的合成及体外抗肿瘤活性研究

目的设计合成积雪草酸衍生物并检测其体外抗肿瘤活性。方法采用计算机辅助药物设计的方法设计并筛选目标化合物的结构;以天然产物积雪草酸为起始原料,对其C-2、C-3、C-23位羟基以及C-28位羧基进行结构改造;采用MTT法测试目标化合物对人肝癌细胞(HepG2)和人肺癌细胞(A549)的体外抗肿瘤活性。结果目标化合物对这两种细胞株的抑制活性均优于母体积雪草酸,其中化合物Ⅰ_8和Ⅱ_2表现出较强的抗肿瘤活性,且分子对接模拟也显示化合物Ⅰ_8和Ⅱ_2与Survivin蛋白的结合力较强。结论经结构改造后的积雪草酸衍生物具有一定的抗肿瘤活性,值得进一步研究。     

鬼臼毒素衍生物的合成及其体外抗肿瘤活性

目的 获得更高活性且具有抗多药耐药活性的抗肿瘤新化合物。方法 将4β-氨基-4-脱氧鬼臼毒素与醇类化合物以丁二酸为桥连接合成了7个鬼臼毒素衍生物,其结构经1H-NMR、TOF-MS证实。用K562和K562/AO2细胞经MTT法筛选了这些衍生物的体外抗肿瘤活性。结果 7个化合物均为新化合物,其中5b、5d的抗肿瘤活性显著高于VP-16, 并且5b、5c、5d、5e的抗多药耐药活性显著高于VP-16。结论 这些鬼臼毒素衍生物可提高抗肿瘤活性。     

Synthesis andin vitro antibacterial activity of quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety

Several oxazolidinones having amine moiety were prepared to form a quaternary ammonium salt with cephalosporin nucleus, and antibacterial activity of the quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety were examined particularly with expectation of dual activity. However, the cephalosporin-oxazolidinone compounds revealed rather weaker antibacterial activity in vitro than their parent oxazolidinone and cephalosporin without showing any characteristic activity as expected.     

Synthesis andin vitro cytotoxicity of 2-alkylaminosubstituted quinoline derivatives

Eight 2-alkylaminosubstituted 5,8-dimethoxy-4-methylquinolines and nine 2-alkylaminosubstituted or 2,6-disubstituted 4-methylquinoline-5,8-diones were synthesized and evaluated in vitro cytotoxicity against four human cancer cell lines (HOP62, SK-OV-3, HCT15 and SF295).     

聚乙二醇缀合熊果酸衍生物的合成及体外抗癌活性

目的:合成具有一定水溶性的聚乙二醇(PEG)缀合熊果酸衍生物并考察其体外抗癌活性。方法:以熊果酸(ursolic acid,UA)作为母核,采用PEG、琥珀酸对其C28位进行接合修饰,合成一系列PEG缀合熊果酸衍生物并考察其水溶性和抗癌活性;采用流式细胞术探讨其抗癌机制。结果:所合成系列PEG缀合熊果酸衍生物的水溶性较熊果酸有明显改善,同时具有更显著的体外抗癌活性;化合物8c对5株受试肿瘤细胞的IC50(48 h)均小于10μmol.L-1,将AGS细胞阻滞于G2/M期并具有诱导凋亡作用(凋亡率高于70%)。结论:将熊果酸C28位进行PEG修饰是保持和提高其抗癌活性的有效途径之一。     

司他夫定衍生物的合成及抗肿瘤活性评价

目的设计合成一系列司他夫定类衍生物,并评价其抗肿瘤活性。方法以司他夫定为原料,经磺酸酯化后与叠氮化钠反应生成5'-叠氮基司他夫定,再通过Huisgen 1,3-偶极环加成反应得到目标化合物。采用MTT法分别以人肝癌细胞(BEL-7402)、人胃癌细胞(BGC-823)、肺癌细胞(A549)为测试细胞株对目标化合物进行体外抗肿瘤活性评价。结果与结论合成了14个5'-脱氧司他夫定衍生物,目标化合物的结构经核磁共振氢谱和碳谱确证。其中化合物4k对人肝癌细胞(BEL-7402)、人胃癌细胞(BGC-823)、肺癌细胞(A549)具有中等的抑制作用。     

Studies on the synthesis andin vitro anti-tumor activity of dihydroberberine derivatives

Three types of dihydroberberine derivatives such as spirobenzylisoquinoline, benzindenoazepine and cyclopropanated quinolizine species were synthesized from dihydroberberine for the investigation on their anti-tumor activity. Among them, cyclopropanated quinolizine species were more effective than spirobenzylisoquinoline and benzindenoazepine against P-388 and L-1210 leukemia cell.     

多取代三氮唑类化合物的合成及其抗肿瘤活性研究

目的设计合成一系列4-胺甲酰-1,5-双芳基-1,2,3-三氮唑类化合物,并评价其抗肿瘤活性。方法以叠氮化钠为原料,经亲核取代反应制成有机叠氮化物后与丙炔酸甲酯通过Huisgen 1,3-偶极环加成反应得到5-碘代-1,2,3-三氮唑,再与单质硫和苄溴类化合物经3步连续反应"一锅法"得到1-对甲氧基苄基-4-甲氧甲酰-5-苄基硫醚-1,2,3-三氮唑,对三氮唑环上的4-甲氧甲酰基进行胺解反应得到目标化合物。采用MTT法测定目标化合物对人乳腺癌细胞(MCF-7)、肝癌细胞(Hep G2)、肺癌细胞(A549)和宫颈癌细胞(He La)的抑制活性。结果与结论合成了15个未见报道的4-胺甲酰-1,5-双芳基-1,2,3-三氮唑类化合物,其结构经1H-NMR、13C-NMR及HR-MS谱确证。其中,化合物7a对Hep G2、A549和He La细胞均表现出中等程度的抑制活性(IC50值分别为23.00、33.88、26.66μmol·L-1),有进一步研究的价值。     

新型槲皮素衍生物的合成及其抗肿瘤活性研究

目的 设计并合成以槲皮素为母核,研究3′-位羟基引入芳香丙烯基槲皮素衍生物的体外抗肿瘤活性。方法 以槲皮素为原料,用不同取代的芳香丙烯酸与其3′-位羟基缩合成酯,得目标槲皮素衍生物,并通过核磁共振波谱仪(¹H-NMR)进行结构表征,同时用噻唑蓝比色法(MTT法)测试目标化合物对不同肿瘤细胞的抗肿瘤活性。结果 通过抗肿瘤活性测试显示,所合成的目标化合物对人结肠癌细胞和乳腺癌细胞表现出了较好的抗肿瘤活性,均达到了微摩尔级,其中化合物5C₁和5C₆对乳腺癌肿瘤细胞的细胞毒达到了10微摩尔级,半抑制浓度(IC₅₀)分别为10.59 μmol/L和10.31 μmol/L。结论 该系列槲皮素衍生物的合成为后续槲皮素衍生物的合成研究和获得具有潜在抗肿瘤活性的先导化合物奠定了基础。     

13-酰胺基取代苦参碱衍生物的合成及抗肿瘤活性研究

目的 合成13-酰胺基取代苦参碱衍生物及研究该类化合物的体外抗肿瘤活性。方法 以槐果碱为原料,通过迈克尔加成（Michael addition）,叠氮还原酰化反应,制得系列13-位酰胺取代的衍生物,所有化合物结构均经¹H NMR等谱确证;选取人肝癌细胞（BEL-7404）和小鼠黑色素瘤细胞（K111）对所合成的目标化合物进行体外抗肿瘤药理活性筛选。结果 设计合成了9个新化合物,大多数化合物对两株肿瘤细胞都具有较强的抑制活性。结论 化合物4b和4e对人肝癌细胞（BEL-7404）有较强的抑制活性。     

Synthesis and antitumor activity of 3-arylisoquinoline derivatives

In order to study the structure-activity relationship of 7,8-dimethoxy-2-methyl-3-(4,5-methylen-edioxy-2-vinylphenyl)isoquinoline-1 (2H)-one (2), which has exhibited significant antitumor activity, chemical modifications of2 were performed to yield the corresponding products (3–7). Further systematic uses of an efficient procedure for the synthesis of 3-arylisoquinoline derivatives produced the substituted compounds (9a−9g), which were tested forin vitro antitumor activity against five different human cancer cell lines.     

硫代秋水仙碱衍生物的合成和抗肿瘤活性

目的寻找高效低毒的秋水仙碱抗肿瘤衍生物。方法秋水仙碱首先被转化为硫代秋水仙碱，然后硫代秋水仙碱通过水解得到7-(N-脱乙酰基硫代秋水仙碱)，最后经胺的酰化得到目标化合物。用¹H NMR，IR，MS和HR-MS确证了这些衍生物的结构，MTT法评价了目标衍生物的细胞毒性；用对小鼠肝癌H₂₂和宫颈癌U₁₄的抑制率评价了衍生物的体内抗肿瘤活性。结果合成了12个硫代秋水仙碱新衍生物。结论尽管一些硫代秋水仙碱衍生物的体外细胞毒性强于秋水仙碱，然而小鼠体内抑瘤活性却较低。     

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.     

Synthesis and antitumor activity of quinonoid derivatives of cannabinoids

Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3), and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6. In the 1960s, the oxidized product 4 had been assigned a para-quinone structure, which was later modified to an ortho-quinone. To distinguish between the two possible quinone structures, a detailed NMR investigation was undertaken. The original para-quinone structure was confirmed. X-ray crystallography elucidated the structures of the crystalline 2 and 6. All three compounds displayed antiproliferative activity in several human cancer cell lines in vitro, and quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.