茄呢基氮芥衍生物的合成及生理活性

茄呢基氮芥衍生物的合成及生理活性;氮芥;茄呢醇;合成;生理活性     

N-酰基-N''''-茄呢基哌嗪衍生物的合成及生物活性

以茄呢醇为起始原料和茄呢基哌嗪为单元的N-(2-全乙酰葡萄糖基苯甲酰基)-N'-茄呢基哌嗪(5)和N-(2-葡萄糖基苯甲酰基)-N'-茄呢基哌嗪(6),共6个新茄呢基哌嗪衍生物.其结构经元素分析,IR,1H NMR和MS确证.测试了化合物4c,5,6对三种人癌细胞(Bel-7402,KB,HCT-8)的体外生理活性,初步结果表明化合物6比4c和5对三种所测细胞有更好的抑制效果.     

N-酰基-N′-茄呢基哌嗪衍生物的合成及生物活性

以茄呢醇为起始原料和茄呢基哌嗪为关键中间体合成了 4个N 酰基 N′ 茄呢基哌嗪 ( 4a～ 4d) ,以及 2个含葡萄糖单元的N ( 2 全乙酰葡萄糖基苯甲酰基 ) N′ 茄呢基哌嗪 ( 5 )和N ( 2 葡萄糖基苯甲酰基 ) N′ 茄呢基哌嗪 ( 6) ,共 6个新茄呢基哌嗪衍生物 .其结构经元素分析 ,IR ,1HNMR和MS确证 .测试了化合物 4c ,5 ,6对三种人癌细胞 (Bel 740 2 ,KB ,HCT 8)的体外生理活性 ,初步结果表明化合物 6比 4c和 5对三种所测细胞有更好的抑制效果     

N-茄呢基谷氨酰胺类化合物的合成

在N,N 二环己基碳二酰亚胺存在下,N 苯甲酰 Nα 茄呢基 L 谷氨酰胺酸和N 羟基琥珀酰亚胺反应制成活化酯,然后分别与胺或者氨基酸甲酯盐酸盐反应制得3种新N 茄呢基谷氨酰胺类化合物.这些化合物的结构经IR、1HNMR、MS和元素分析确证.     

3,4,-三甲氧基甲酰茄呢基胺的合成

茄呢醇;3;4;-三甲氧基甲酰茄呢基胺的合成     

酰胺型茄呢醇衍生物的合成与生理活性

酰胺型茄呢醇衍生物的合成与生理活性;N-茄呢基酰胺;N-酰基-N′-茄呢基哌嗪;合成;生理活性     

茄呢基胺类化合物的合成研究(Ⅰ)——N,N-二(酰氧基乙基)茄呢基胺的合成

茄呢基胺类化合物的合成研究(Ⅰ)——N;N-二(酰氧基乙基)茄呢基胺的合成     

N-茄呢基胺类糖酯化合物的合成及生理活性

在氢氧化钠和四丁基溴化铵存在下,将化合物2-N-茄呢基胺基苯甲酸(3)和N-茄呢基己二酰胺酸(6)分别与O-乙酰基溴代葡萄糖、O-乙酰基溴代半乳糖、O-乙酰基溴代乳糖和O-乙酰基溴代麦芽糖反应制得对应的糖酯4a～4d和7a～7d,由元素分析,IR,1H NMR和MS确证了8个新化合物的结构,并对其中6个化合物(4a,4d和7a～7d)在三种癌细胞模型上进行了一些初步体外生理活性的测试.     

N-茄呢基-N,N′-二(3,4-二甲氧基苄基)乙二胺的合成

癌症仍是需要攻克的医学难题之一. 虽然已有多种抗癌剂用于临床,但大多数抗癌剂是以细胞毒性来抑制癌细胞的繁殖,使用剂量受到限制,长期治疗还会产生毒副作用. 研究表明,N-茄呢基-N,N′-二(3,4-二甲氧基苄基)乙二胺(简称SDB-乙二胺)[1]具有优先作用于多种抗药性肿瘤的直接的细胞毒性,对几乎所有类型临床抗肿瘤药物具有增效作用,其中对抗生素类和生物碱类抗癌药物的增效尤为显著,如对其中的博莱霉素(争光霉素)、呱来霉素、磅霉素等,每毫升注射液含有3和10 μg的SDB-乙二胺,药效分别能提高47和130倍,对新制癌菌素(neocarzinostatin)也能提高2倍以上[2]. 与其他增效剂相比,SDB-乙二胺的增效作用具有定向细胞毒性,而本身完全没有细胞毒性,安全性好,可以连续使用,可减少抗癌剂的剂量,减轻毒副作用[3]. 因此,研究开发抗癌药物增效剂是癌症治疗的发展方向之一.     

N-茄呢基-N,N'-二(3,4-二甲氧基苄基)乙二胺的合成

茄呢基溴;;抗肿瘤药;N-茄呢基-N;N'-二(3;4-二甲氧基苄基)乙二胺的合成     

两类氮芥衍生物的合成及其生理活性研究

设计合成了3个苯胺氮芥和6个萘酰亚胺-氮芥衍生物,产物结构均经1H NMR,13C NMR,ESI-MS和元素分析确认.使用MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]法测试了9个化合物对HL-60,K562和SMMC-7721三种...     

长链醇和胺修饰的芳香氮芥衍生物的合成及生理活性

为了研究不同取代基对苯甲酸氮芥抗肿瘤活性的影响,以对氨基苯甲酸为起始原料,设计合成了6个新化合物,目标产物结构经元素分析、1H NMR和MS等确证.采用MTT法对白血病细胞HL-60、白血病细胞K562和肝癌细胞SMMC-7721进行了体外的抗肿瘤活性筛选.活性测试结果表明这些长链醇和胺修饰苯甲酸氮芥后,目标产物的抗肿瘤活性未得到提高,均弱于参照药物美法伦.     

新型氮芥和卤代烷基哌嗪芳香醛的合成

通过对Vilsmeier反应、烷基化反应和氯化反应的改进提出了以简单易得的苯胺和苯基哌嗪为原料制备氮芥和哌嗪芳香醛的方法. 采用该改进的方法合成了8个氮芥和哌嗪芳香醛, 其中7个为新化合物. 它们的结构均经质谱、红外光谱、核磁共振谱和元素分析确证.     

Synthesis and Characterization of Thiophene‐derived Amido Bis‐nitrogen Mustard and Its Antimicrobial and Anticancer Activities

The thiophene‐derived amido bis‐nitrogen mustard N²,N²,N⁵,N⁵‐tetrakis(2‐chloroethyl)‐3,4‐dimethylthiophene‐2,5‐dicarboxamide was designed and synthesized via five‐step reactions from commercially available 2‐chloroacetonitrile. This target compound was confirmed by ¹H NMR, ¹³C NMR, MS, IR spectra and elemental analyses, and its structure was further characterized by X‐ray single‐crystal analysis. The biological activities for the title compound and some intermediates were evaluated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that the title compound could inhibit efficiently the growth of the tested microorganisms including drug‐resistant bacteria MRSA to some extent. Moreover, the target compound was found to be effective against prostatic carcinoma cell line (PC‐3), breast carcinoma cell line (MCF‐7), colon carcinoma (LoVo) and lung cancer (A549). Especially, it gave selective antitumor efficacy against prostatic carcinoma cell line (PC‐3) at a low dose.     

具有抗肿瘤活性甾体氮芥类化合物的研究进展

本文按照甾体的甾核结构对甾体氮芥化合物进行分类,综述了近年来新合成的甾体氮芥类化合物及其衍生物的抗肿瘤活性及研究进展,并对此方面的发展趋势和应用前景作了展望。     

N-(取代苯氨基硫代甲酰基)邻苯二甲酰胺酸的合成

本文用四种硫脲衍生物和一种脲衍生物同邻苯二甲酸杆进行单酰化反应, 筛选了最适宜反应条件, 避免了环状副产物, 合成了N-(取代萃氨基硫代甲酰基)邻苯二甲酸。     

Lethal Effect of Benzene Nitrogen Mustard Glucoside Derivate on K562 Cells

A new synthesized benzene nitrogen mustard was converted into glycosyl donor-trichloroacetimidate that was glycosylated with p-nitrophenol（glycosyl donors） to form β-lactosyl p-nitrobenzene under the protection of acetyl in a stereoselective manner, was prepared and evaluated for its cytotoxicity towards cultured K562 cell line. Methylthiazoy tetrazolium（MTT） assay, transmission electron microscopy（TEM）, flow cytometry（FCM） and immunohistochemistry were utilized to explore the mechanisms of how the compound arrests the growth of HCT-T cells. This new synthesed benzene nitrogen mustard glucoside derivate（BNMGD） presented a lower toxicity to normal cells, but is significantly more toxic to K562 cells compared with nitrogen mustard, meanwhile it can induce the apoptosis of K562 cells. These results indicate that the new synthesized BNMGD can inhibit the growth of K562 cells and induce the apoptosis, and its cytotoxicity towards cultured K562 cell line is much more effective than that of nitrogen mustard.     

Design and Synthesis of Glycosylated Aromatic Nitrogen Mustard Derivatives

Antibody-directed enzyme prodrug therapy(ADEPT) is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol(glycosyl donors) to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.     

4-溴-5-硝基邻苯二甲腈的合成及晶体结构

以邻苯二甲酸酐为原料,经溴化、脱水、亚胺化、硝化、酰胺化、脱水6步反应合成了一种易调变的酞菁前驱体——4-溴-5-硝基邻苯二甲腈,并测定了其晶体结构。