18β-甘草次酸A环开环衍生物的合成及抗肿瘤活性

采用化学方法在18β-甘草次酸A环上进行结构修饰,合成了一系列新颖的A环具有不同官能团的开环衍生物.初步研究了它们对人体肝癌细胞HepG-2的体外细胞毒活性,结果表明,羟基的数目和位置对抑制HepG-2细胞增殖起着重要的作用.     

18β-甘草次酸吡啶酰胺衍生物的定向合成及其初步抗癌活性研究

以18β-甘草次酸和2,5-吡啶二甲酸为起始原料,便捷地合成了5种含吡啶杂环多酰胺结构的18β-甘草次酸衍生物.全部新合成化合物的结构由1H NMR,13C NMR及HRMS等方法得到了确证.通过四甲基偶氮唑盐(MTT)法对所有新合成化合物的抑制人宫颈癌Hela细胞活性进行了体外评价,初步发现目标系列化合物对人宫颈癌Hela细胞均具有细胞毒活性,能够有效抑制Hela细胞增殖、诱导其凋亡,IC50最小值仅为0.02μmol·L-1,均优于临床抗肿瘤药物阿糖胞苷.     

甘草次酸衍生物的合成及其抗癌活性

设计合成了6种甘草次酸衍生物,用元素分析、波谱分析鉴定了它们的结构,并比较了它们的体内、体外抗癌活性,均表现出较好的活性,尤其是化合物Ⅰa,Ⅰb口服效果比盐酸氮芥还好,表现出甘草次酸对氮芥有明显的增效应用。     

甘草次酸衍生物的合成

豆科植物甘草中含有大量甘草次酸(Glycyrrhetinic Acid)。近代药理实验表明,甘草的抗炎症、抗溃疡以及抗变态反应等功效,主要归因于甘草中所含的甘草甜素,甘草次酸及其衍生物。多年来,国内外学者对甘草次酸     

甘草次酸衍生物的合成

以甘草次酸为原料,合成了4个甘草次酸衍生物.其结构经<'1>H NMR,IR和MS确证.     

新型甘草次酸酰胺杂环衍生物的合成及其抗结核活性

以18β-甘草次酸为原料,经过多步酰胺化反应合成了14个含不同杂环的新型甘草次酸多酰胺衍生物(11a～11n),收率78.6%～92.3%,其结构经1H NMR,13C NMR和IR表征。其中11i和11n的初步抑菌活性测试结果表明,杂环酰胺基团对甘草次酸衍生物的抗结核活性具有明显的增效作用。     

新型18β-甘草次酸氨基二硫代甲酸酯衍生物的合成及抗癌活性研究

以18β-甘草次酸为原料首先经简单酰胺化反应方便地得到18β-甘草次酸哌嗪,再与二硫化碳、碳酸钾以及不同结构卤代烃"一锅煮"法快速、高效地合成了10种含氨基二硫代甲酸酯结构的新型甘草次酸酰胺类衍生物,通过IR,1H NMR,13C NMR和HR-MS对所有新化合物进行了结构确证;并以四甲基偶氮唑盐比色法(MTT)法评价了该类化合物对人肝癌细胞株SMMC-7721的细胞毒活性.初步生物活性研究结果表明,该类化合物具有明显的抑制人肝癌细胞增殖、诱导其凋亡的细胞毒活性,给药72 h,半抑制浓度IC50最优值仅为14.42μg/mL.     

甘草次酸及其衍生物的质谱研究

本文通过应用ＥＩ质谱和高分辨质谱对甘草次酸及其衍生物进行研究，阐明了分子离子的各种裂解、重排机理，讨论了主要离子的形成过程以及不同取代基对分子离子峰强度的影响。并用软电离手段──快原子轰击正、负离子（ＰＦＡＢ和ＮＦＡＢ）质谱，使ＥＩ谱上不出现分子离子峰的两个化合物而获得满意结果。     

齐墩果酸衍生物的合成及抗肿瘤活性研究

以天然产物齐墩果酸为先导化合物,经过氧化、酯化(酰化)、水解等反应合成了8个齐墩果酸衍生物,以MCF-7和A549细胞为靶细胞,紫杉醇和吉非替尼为阳性对照物,采用磺酰若丹明B(SRB)法进行初步的体外抗肿瘤活性筛选。结果表明,化合物5a对A549细胞的抑制作用与母体齐墩果酸相当,化合物5d对A549细胞的抑制活性明显高于母体齐墩果酸。因此,化合物5a和5d值得进一步研究。     

新型藤黄酸衍生物的合成及其抗肿瘤活性

以藤黄酸(1)为原料,分别与HBr和有机胺反应,合成了9个新型的藤黄酸衍生物(2~6),其结构经1HNMR,MS和HR-MS表征。采用MTT法测定了2~6对人结肠腺癌细胞(RKO)、人肝癌细胞(HepG-2)和人卵巢腺癌细胞(OVCAR-3)的体外抗肿瘤活性。结果表明,藤黄酸(N-丙基对甲苯磺酰胺)酯3,藤黄酸(N-丙基苯丙酰胺)酯4和N-色胺藤黄酰胺6b的抗肿瘤活性显著高于1;33-羟基转位藤黄酸2的抗肿瘤活性则大大降低。     

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

With chenodeoxycholic acid as starting material,a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined.Among the synthesized derivatives,compounds 6 and 18 displayed distinct antiproliferative activity against PC-3,H-292,SKBR3 and Hey-1B cancer cells,and compounds 10,17 and 18 showed significant antiproliferative activity against SKBR3 cells.Our results reveal that the position of hydroximino on ring A or B of the parental scaffold dramatically affects the antiproliferative activity of these compounds.The conversion of 7-hydroximino to other substituent or 7-hydroximino to 3-hydroximino in the compounds resulted in a dramatic decrease of the antiproliferative activity,suggesting the importance of 7-hydroximino group for the biological activity of the compounds.The structure/activity correlation generated from the studies provides valuable information for the further design of novel chemotherapeutic drugs.     

川芎嗪芳酸衍生物的合成及抗血小板聚集活性

以具有活血化淤作用的中药有效成分川芎嗪、阿魏酸为先导物, 按药物化学拼合原理, 设计合成了6个全新结构的川芎嗪芳酸衍生物, 其结构经IR, 1H NMR, 13C NMR及MS确证. 体外药效筛选结果显示, 部分川芎嗪芳酸衍生物对二磷酸腺苷(ADP)诱导的血小板聚集具有较好的抑制活性, 其中川芎嗪阿魏酸拼合物(1a)的抑制活性是奥扎格雷的5.7倍.     

Synthesis and Anti-tumor Activity of Novel Glycyrrhetinic Acid Derivatives

Twenty-five derivatives of glycyrrhetinic acid(GA)modified on the A-ring,at C30 and C11 positions were synthesized.Their in vitro cytotoxicity against various cancer cell lines[henrietta lacks strain o...     

2β-羟基熊果酸的合成及其抗肿瘤活性

以熊果酸为原料,经C-3羟基氧化、C-28羧基苄酯化保护、C-2乙酰化及水解、还原、脱保护得到2β-羟基熊果酸,6步反应的总收率为60.1%。 中间体及目标化合物结构经IR、1H NMR、13C NMR和MS测试技术确证。 以噻唑蓝(MTT)比色法检测2β-羟基熊果酸对人白血病细胞K562及人肺癌细胞A549肿瘤细胞的体外抑制活性,结果表明,对2种肿瘤细胞的生长均表现出一定的抑制作用。     

新型芳基修饰的藤黄酸衍生物的合成及其抗肿瘤活性

以取代酚或羟基吡啶为原料,在无水碳酸钾存在下,与溴代醇发生威廉姆森醚合反应制得中间体--芳（杂环）氧基醇(2a~2k); 2a~2k分别与藤黄酸通过光延反应合成了藤黄酸衍生物（3a~3k）。以DDC/HOSu为偶联剂,芳酸与3-氨基-1-丙醇经偶联反应制得中间体--芳酰氨基醇（5a~5h）; 5a~5h分别与藤黄酸通过光延反应合成了藤黄酸衍生物（6a~6h）。 2, 3, 5和6为新化合物,其结构经¹H NMR, ESI-MS和HR-MS表征。采用MTT法测定了3和6对肺腺癌细胞(A549)、肝癌细胞(HepG-2)和乳腺癌细胞(SK-BR-3)的体外抗肿瘤活性。结果表明：部分化合物对肿瘤细胞的抑制活性明显高于藤黄酸。     

Grafting of 18β-Glycyrrhetinic Acid and Sialic Acid onto Chitosan to Produce a New Amphipathic Chitosan Derivative: Synthesis,Characterization, and Cytotoxicity

Chitosan is the only cationic polysaccharide found in nature. It has broad application prospects in biomaterials, but its application is limited due to its poor solubility in water. A novel chitosan derivative was synthesized by amidation of chitosan with 18β-glycyrrhetinic acid and sialic acid. The chitosan derivatives were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and measurement of the zeta potential. We also investigated the solubility, cytotoxicity, and blood compatibility of chitosan derivatives. 18β-glycyrrhetinic acid and sialic acid could be grafted onto chitosan molecular chains. The thermal stability of the synthesized chitosan derivatives was decreased and the surface was positively charged in water and phosphate-buffered saline. After chitosan had been modified by 18 β-glycyrrhetinic acid and sialic acid, the solubility of chitosan was improved greatly in water and phosphate-buffered saline, and percent hemolysis was <5%. Novel amphiphilic chitosan derivatives could be suitable polymers for biomedical purposes.     

Synthesis of Phenoxazinone Derivatives and Antiproliferative Activities on Wild-type and Drug-resistant Tumor Cells

Some natural occurring phenoxazinones, such as xanthommatin, actinomycin D (AMD), and questiomycin A (APO), all contain a coplanar tricyclic iminoquinone system (Figure 1). Polycyclic iminoquinone is an important chemical structural moiety of action- mycins and other antitumor drugs. One of the cytostatic mechanisms of coplanar polycyclic compounds, that they can intercalate into human DNA, to cause enzymatic blocking and reading errors during the replication process. AMD is a well known…     

Synthesis of Aminoalkyl-substituted Polymethoxychalcone Derivatives and Their Antiproliferative Activities Against Three Human Cancer Cell Lines

Two novel series of sixteen aminoalkyl-substituted polymethoxychalcone derivatives 2a-2h and 3a-3h were synthesized from 2'-hydroxy-3,4,5,4',6'-pentamethoxy chalcone(1) through extending alkoxy side chain at the 2'-position, and introducing amine hydrogen bond receptor at the end of the side chain. The structures of all the synthesized compounds were confirmed by ¹H NMR, ¹³C NMR and MS techniques. Furthermore, all the compounds were tested for antiproliferative activities in vitro against a panel of three human cell lines(HeLa, HCC1954 and SK-OV-3) via CCK-8 assay. The results show that all the target compounds exhibit antiproliferative activities against the three human cancer cells with IC₅₀ values of 4.62-48.21 μmol/L, except compound 2h against SK-OV-3 cells. Most of these compounds were more active when compared to the positive control cis-Platin.     

3-哌啶甲酸及其衍生物的合成与应用研究进展

3-哌啶甲酸及其衍生物是重要的药物中间体, 具有很高的生物活性. 综述了3-哌啶甲酸及其羧基酯化、不饱和、不同位置取代与多取代衍生物的合成方法, 并对3-哌啶甲酸及其衍生物在合成γ-氨基丁酸(GABA)摄入抑制剂、抗肿瘤药、生长激素促分泌素、消炎药物、心血管药物、促智药物、抗流感病毒、骨疾病等药物中的应用进行了概述.