新的4’-去甲表鬼臼衍生物的合成及其抗癌活性

根据鬼臼毒衍生物和5-氟尿嘧啶的抗癌机理和构效关系，合成了7个新的4β- 5-氟尿嘧啶取代-4’-去甲表鬼鬼臼毒衍生物。在抑制金属基质蛋白酶I和胶原酶I 活性测试中，化合物2.4和2.6的抑制活性比鬼臼乙叉甙（VP-16）和5-氟尿嘧啶（ 5-Fu）强的3倍和5倍，在治疗癌细胞转移方面值得进一步探讨。     

新的4＇-去甲表鬼臼衍生物的合成及其抗癌活性

根据鬼臼毒衍生物和5-氟尿嘧啶的抗癌机理和构效关系,合成了7个新的4β-5-氟尿嘧啶取代4＇-去甲表鬼臼毒衍生物.在抑制金属基质蛋白酶I和胶原酶I活性测试中,化合物2.4和2.6的抑制活性比鬼臼乙叉甙(VP-16)和5-氟尿嘧啶(5-Fu)强3倍和5倍,在治疗癌细胞转移方面值得进一步探讨.     

新的4′-去甲表鬼臼衍生物的合成及其抗癌活性

根据鬼臼毒衍生物和 5 氟尿嘧啶的抗癌机理和构效关系 ,合成了 7个新的 4β 5 氟尿嘧啶取代 4′ 去甲表鬼臼毒衍生物 .在抑制金属基质蛋白酶I和胶原酶I活性测试中 ,化合物 2 .4和 2 .6的抑制活性比鬼臼乙叉甙 (VP 16 )和5 氟尿嘧啶 (5 Fu)强 3倍和 5倍 ,在治疗癌细胞转移方面值得进一步探讨 .     

鬼臼及其羧酸酯类化合物2位立体异构体的EI MS质谱研究

鬼臼(podophyllotoxin)及其衍生物在抗癌方面表现出良好的活性。最近,Lopez-perez等人研究了合成的鬼臼羧酸酯类化合物的细胞活性,发现鬼臼的4位降冰片烯酯化合物在对P-388,A-549,HT-29和MEL-28有较母体鬼臼强3~5倍的活性[1],因此引起了人们对鬼臼酯类化合物抗癌活性与结构特点     

电化学法研究苯磺酰类5-氟尿嘧啶衍生物与双链和G-四链DNA的相互作用

本文以自组装法制得的双链DNA（ds．DNA）和G-四链体DNA（G4-DNA）修饰的金电极为工作电极,以Fe（CN）63-／4-为电活性指示剂,采用循环伏安法和微分脉冲伏安法研究了非电活性苯磺酰类5-氟尿嘧啶衍生物与ds-DNA和G4．DNA的相互作用．实验结果表明：苯磺酰类5-氟尿嘧啶与ds-DNA或G4．DNA的结合常数与苯环上邻、对位取代基的得失电子能力密切相关,强吸电子基团取代有利于苯磺酰类5-氟尿嘧啶选择性结合G-四链体DNA．     

间氯苯基锰卟啉-5-氟尿嘧啶配合物的合成及其对癌细胞的抑制活性

合成了4种新5-氟尿嘧啶-卟啉衍生物：5-[3-(2-(5-氟尿嘧啶-1-基)乙氧基)苯基]-10,15,20-三(3-氯苯基)卟啉(1a)、5-[3-(2-(5-氟尿嘧啶-1-基)乙氧基)苯基]- 10,15,20-三(3-氯苯基)锰卟啉(2a)、5-[3-(3-(5-氟尿嘧啶-1-基)丙氧基)苯基]-10,15,20-三(3-氯苯基)锰卟啉(2b)和5-[3-(4-(5-氟尿嘧啶-1-基)丁氧基)苯基]-10,15,20-三(3-氯苯基)锰卟啉(2c),通过UV-Vis、IR、MS及元素分析表征了它们的结构。 用噻唑蓝法（MTT法）测定了化合物2a、2b和2c对人胃癌细胞株BGC-823的抑制活性。 化合物2b的半数抑制浓度IC50为1.34 μmol/L,表明有一定的细胞毒作用。     

1,3-取代吲哚-2-酮衍生物的合成与肿瘤细胞毒活性研究

以苯胺为原料,通过肟化、环合生成二氢吲哚-2,3-二酮,再对其进行N-烷基化、亲核加成和磺酰化反应得到目标化合物5a～5g和7a～7e。通过¹H NMR、¹³C NMR确认其结构。采用噻唑蓝（MTT）法测试了目标化合物对乳腺癌细胞MDA-MB-231、鼠黑色素瘤细胞B16、鼠结肠癌细胞CT26三种肿瘤细胞的体外抑制活性。结果表明,化合物7d、7e具有明显的肿瘤细胞毒活性,其中化合物7d对MDA-MB-231的细胞毒活性比阳性药五氟尿嘧啶更强,IC₅₀为4.63±0.14μmol/L。本文结果可为进一步研究具有肿瘤细胞毒活性的吲哚酮类衍生物提供参考。     

两种含氮类大豆苷元衍生物对人体红细胞的抗溶血作用

合成了2种含氮类大豆苷元衍生物,4,7-二（（甘氨酸钠）羰基）甲氧基异黄酮（L1）和4'',7-二（肼羰基）甲氧基异黄酮（L2）并用元素分析、红外光谱和核磁共振氢谱对其进行了表征。研究了大豆苷元衍生物的抗氧化性能,评价了其对自由基、超氧阴离子自由基的吸附能力,以及对人体血红细胞抗氧化损伤的保护作用。实验结果表明,大豆苷元衍生物在生理pH条件下的抗氧化活性优于维生素C,特别是在清除羟自由基和抑制人血红细胞溶血方面,大豆苷元衍生物抗氧化能力表现更为突出。大豆苷元衍生物的羟自由基清除活性IC₅₀值是维生素C的104倍。     

新型天麻素衍生物的设计、合成及抗肿瘤活性研究

以顺丁烯二酸酐为原料,依次经加成和取代反应制得一系列斑蝥素衍生物（3a~3c）;以葡萄糖为原料,经乙酰化、溴化和甲基化反应制得乙酰天麻素（7）; 7与3a~3c经酯化反应合成了一系列新型天麻素衍生物（8a~8c）;以5-氟尿嘧啶为原料,合成了新型天麻素衍生物（11）,其结构经¹H NMR, ¹³C NMR, IR和MS（ESI）表征。采用细胞增殖抑制实验法（MTT法）研究了8a~8c和11对肝癌细胞（HepG2和SMCC7721）的抑制活性。结果表明：8a, 8b, 8c和11对肝癌细胞株均有一定的抑制作用,其中8a的抑制活性最好,其IC₅₀为55.33 μmol·L^-1（HepG2）和42.07 μmol·L^-1（SMCC7721）。     

含1,2,4-三唑双席夫碱衍生物的合成、抗菌活性及分子对接

以3, 5-二氨基-1,2,4-三唑与取代苯甲醛为原料成功合成了5种1,2,4-三唑双席夫碱衍生物（D1-D5）。采用菌丝生长速率法和分子对接技术研究了化合物对小麦赤霉病菌的体外抗真菌活性。结果表明,除化合物D3外,其余4种化合物的活性均优于对照药物氟康唑,其中化合物D1的抑制效果约为对照药物的1.8倍,可作为抗小麦赤霉病菌的先导化合物进一步研究。分子对接的结果与生物活性一致,即对接结合能越小,抗小麦赤霉病菌的活性越强,且氢键是维持药物分子与受体蛋白稳定结合的关键因素。为克服病原菌的耐药性问题,研究了活性最强的化合物D1和D2与氟康唑复配体系的抑菌作用,结果发现,m(D1)∶m（氟康唑）=1∶2、m(D2)∶m（氟康唑）=1∶1、1∶2、1∶4和4∶1时,共毒系数（CTC）值大于120,表现为增效作用,故化合物D2有望成为一种具有应用前景的复配用剂。     

含5-氟尿嘧啶的氨基酸衍生物的合成及其抗肿瘤活性研究

5-氟尿嘧啶乙酸对硝基苯酯和5-氟尿嘧啶丙酸对硝基苯酯与一系列氨基酸反应,制备了12个新的含5-氟尿嘧啶的氨基酸衍生物,并确定了化合物的结构。初步动物试验表明某些化合物有一定的抗肿瘤活性。     

含氨基酸席夫碱的5-氟尿嘧啶衍生物的合成及其抗肿瘤活性

以N 1-(2-四氢呋喃烷基)-5-氟尿嘧啶为原料, 与1,4-二溴丁烷反应, 得到N¹-(2-四氢呋喃烷基)-N³-(4-溴丁基)-5-氟尿嘧啶(2), 最后与氨基酸席夫碱的钾盐缩合, 得到13个新的目标化合物3. 其结构经IR, ¹H NMR, MS和元素分析确证. 初步的体外抗肿瘤试验结果表明, 目标化合物具有一定的抗肿瘤活性.     

Synthesis and antitumor activity of N1-acetylamino-(5-alkyl/aryl-1,3,4-thiadiazole-2-y1)-5-fluorouracil derivatives

A new series of N1-acetylamino-(5-alkyl/aryl- 1,3,4-thiadiazole-2-y1)-5-fluorouracil derivatives were designed and synthesized.These compounds have not been reported in literature,and their structure chemical were confirmed by IR,1H NMR and MS (HRMS).The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.     

Synthesis and antitumor activity of N^1-acetylamino-（5-alkyl/aryl-1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives

A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.     

5-氟脲嘧啶的D-氨基葡萄糖衍生物的合成及其抗肿瘤活性的研究

以α-氨基酸为连接基,将5-氟脲嘧啶同D-氨基葡萄糖键连合成了4种新的5-氟脲嘧啶的衍生物,并确认了它们的结构。体外抗肿瘤活性实验结果表明:链连的D-氨基葡萄糖使5-氟脲嘧啶的抗肿瘤活性有明显的提高,表明它们之间可能存在着某种抗肿瘤的协同作用。     

Synthesis and bioevaluation of 5-fluorouracil derivatives

A series of six novel 5-fluorouracil derivatives 1-6 were synthesized and their structures confirmed by (1)H- and (13)C-NMR, MS and elemental analysis. The preliminary in vitro antitumor activities against B16, K562 and CHO cells and the in vivo inhibitions of liver cancer H(22) demonstrated that some of these compounds effectively inhibit the growth of tumor cells, but the in vivo trials in mice revealed that the compounds also exhibited serious liver and lung tissue toxicity. The hydrolysis experiments indicated that this type of compound did not readily liberate 5-fluorouracil, as expected.     

5-Fluorouracil derivatives XXIII. Synthesis and antitumor activities of 1-carbamoyl-5-fluorouracils having aromatic ring

In order to get good antitumor agents especially better than 5-fluorouracil, tegafur and l-hexylcarbamoyl-5-fluorouracil (HCFU), fourty nine 1-carbamoyl-5-fluorouracil having aromatic ring were synthesized from 5-fluorouracil and isocyanates or mines. Antitumor activity was tested in the L1210 tumor system, and 5 compounds gave better value of therapeutic ratio than 5-fluorouracil, tegafur, HCFU. 1-(4-Methoxybenzylcarbamoyl)-5-fluorouracil gave the best result.     

三唑类白杨素衍生物的设计、合成及其抗增殖活性研究

合成了2个系列的白杨素衍生物,采用噻唑蓝(MTT)法测试了所有化合物针对六种肿瘤细胞的体外抗增殖活性,包括MGC-803, BEL-7402, HepG2, HeLa, A549以及SGC-7901细胞.实验结果显示, 7-[1-(3-氟苯基)-1H-1,2,3-三唑-4-甲氧基]-白杨素(1c)与7-[1-(2-氯苯基)-1H-1,2,3-三唑-4-甲氧基]-白杨素(1g)针对MGC-803细胞的活性与先导化合物白杨素及阳性对照药5-氟尿嘧啶相比显著提高.因此,化合物1c与1g具有深入研究用以开发抗癌药物的潜能.     

Synthesis of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils,and cytosine

The cis and trans isomers of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils, and cytosine were obtained by alkylation of 2,4-bis(trimethylsilyl) derivatives of uracil, 5-substituted uracils, and cytosine with 2,3-dihalotetrahydrofurans. 2,3-Anhydro compounds are also formed in the alkylation of 5-halouracil derivatives. The physicochemical properties of the compounds obtained and the antineoplastic activities of the 5-fluorouracil derivatives were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 94–99, January, 1987.     

Synthesis of 1- and 3-arylcarbonyl derivatives of 5-fluorouracil

4′-Substituted 1-arylcarbonyl-5-fluorouracil derivatives were synthesized from the reaction of the potassium salt of 5-fluorouracil with one equivalent of aryl acid chloride in acetonitrile. 4′-Substituted 3-arylcar-bonyl-5-fluorouracil derivatives were synthesized from the reaction of 5-fluorouracil with 3 equivalents of the aryl acid chloride in pyridine and the subsequent hydrolysis of the 1,3-diarylcarbonyl-5-fluorouracil derivatives in situ with a small amount of water. If a large amount of water were used in the second step, the 1,3-diarylcarbonyl-5-fluorouracil precipitated before it hydrolyzed. The melting behaviors of both the 1-arylcarbonyl-5-fluorouracil and 3-arylcarbonyl-5-fluorouracil series suggested that thermal decomposition or rearrangement occurred on heating. The position of the C⁶-H absorption in the ¹H nmr spectra of 1-arylcarbonyl-5-fluorouracils was 0.14 to 0.23 ppm farther downfield than that of the corresponding 3-arylcarbonyl-5-fluorouracils while that of the 1,3-diarylcarbonyl-5-fluorouracils was even farther downfield. The Rf values of 1-arylcarbonyl-5-fluorouracils were significantly greater (0.23 to 0.41) than those of the corresponding 3-arylcarbonyl-5-fluorouracils, while that of 1,3-diarylcarbonyl-5-fluorouracil was slightly greater than that of 1-arylcarbonyl-5-fluorouracils.