衍生合成七种氮杂糖成分及其抑制α-葡萄糖苷酶构效关系分析

以白树(Suregada glomerulata)中分离得到的五个氮杂糖成分为底物,在其N上衍生合成,分析N上衍生基团对α-葡萄糖苷酶抑制活性的影响。分别合成了N-甲基化、N,N-二甲基化、N-丁基化和N-氧化衍生物,体外测试化合物的α-葡萄糖苷酶抑制活性。合成了7个未见文献报道的目标化合物,结构经1HNMR、13CNMR和MS确证。初步药理结果显示,所有衍生物均未见增强α-葡萄糖苷酶抑制活性。N-取代基对活性的影响较大;化合物5属于N,N-二取代衍生物,仍具有一定的α-葡萄糖苷酶抑制活性,值得进一步研究。     

一种植物生长激素-N'-(5-硝基-2-羟基苯亚甲基)-3,5-二羟基苯甲酰肼的合成、晶体结构和抗菌活性

目的:合成并表征一种属于植物生长激素的席夫碱类化合物.方法:由5-硝基水杨醛和3,5-二羟基苯甲酰肼在甲醇溶液中反应得到N′-(5-硝基-2-羟基苯亚甲基)-3,5-二羟基苯甲酰肼.结果:用单晶X-射线衍射法测得其结构并表征,同时通过抗菌实验证明其在一定浓度下具有明显的抗菌活性.结论:这种席夫碱类化合物在某种程度上具有明显的抗菌活性.     

岩白菜素两个衍生物的合成及镇痛活性研究

本文研究两个岩白菜素衍生物的合成及其镇痛活性.以岩白菜素为原料,通过选择性磺酰化和曼尼希反应各自得到一个产物.采用小鼠扭体法检测两个化合物的镇痛活性.两个化合物分别在剂量为60 mg/kg,100 mg/kg时可明显抑制小鼠扭体次数,试药组与生理盐水组比较差异具有显著性意义(P<0.05).对比两衍生物的结构提示镇痛活性可能与岩白菜素的基本骨架有关.     

三七二醇型皂苷元磺酰胺类衍生物的合成及抗肿瘤活性研究

本研究以三七二醇型皂苷为原料,通过琼斯氧化得到化合物1,再将化合物1的3位羰基经还原胺化反应转化为氨基得到化合物2,再用化合物2与磺酰氯类试剂反应得到化合物3~12,合成了11个未见文献报道的目标化合物,其结构均经过核磁共振、质谱确证。采用MTS法评价这些化合物对人白血病细胞株HL-60、肝癌细胞株SMMC-7721、肺癌细胞株A-549、乳腺癌细胞株MCF-7、结肠癌细胞株SW480等肿瘤细胞株的抗肿瘤活性。药理活性评价结果显示,化合物9有一定的抗肿瘤活性,值得进一步研究。     

新的药根碱三唑的合成与抗菌以及乙酰胆碱酯酶抑制活性评价北大核心CSCD

通过有机合成手段合成了四个新的含三唑的药根碱衍生物,利用1H NMR,13C NMR和MS确认了目标化合物的结构,对合成的化合物进行了抗菌和抑制乙酰胆碱酯酶(ACh E)和丁酰胆碱酯酶(Bu Ch E)的活性测试。目标化合物显示具有较好的抗菌活性,抗菌结果显示所制备的化合物抑菌MIC范围从1到64μg/m L,对一些敏感菌的活性和阳性药物罗红霉素相当。对乙酰胆碱酯酶(ACh E)的抑制也表现出较好的活性,IC50值从0.46μM到0.86μM,但这些化合物对丁酰胆碱酯酶(Bu Ch E)表现出较弱的活性IC50>100μM。药根碱三唑具有较好的抑制乙酰胆碱酯酶的活性,且具有较好的选择性,同时具有较好的抗菌活性而且拓展了抗菌谱,可能成为一种新型的抗菌和治疗老年痴呆的先导化合物。     

新的药根碱三唑的合成与抗菌以及乙酰胆碱酯酶抑制活性评价

通过有机合成手段合成了四个新的含三唑的药根碱衍生物,利用1H NMR,13C NMR和MS确认了目标化合物的结构,对合成的化合物进行了抗菌和抑制乙酰胆碱酯酶(ACh E)和丁酰胆碱酯酶(Bu Ch E)的活性测试。目标化合物显示具有较好的抗菌活性,抗菌结果显示所制备的化合物抑菌MIC范围从1到64μg/m L,对一些敏感菌的活性和阳性药物罗红霉素相当。对乙酰胆碱酯酶(ACh E)的抑制也表现出较好的活性,IC50值从0.46μM到0.86μM,但这些化合物对丁酰胆碱酯酶(Bu Ch E)表现出较弱的活性IC50100μM。药根碱三唑具有较好的抑制乙酰胆碱酯酶的活性,且具有较好的选择性,同时具有较好的抗菌活性而且拓展了抗菌谱,可能成为一种新型的抗菌和治疗老年痴呆的先导化合物。     

5-氯水杨醛缩2，4-二羟基苯酰肼的合成及其抗菌活性的研究

目的合成5-氯水杨醛缩2,4-二羟基苯酰肼,对其进行结构表征,并测定其抑菌活性。方法运用席夫碱合成原理,合成目标产物,通过单晶衍射分析确定其分子结构。采用试管法和平板法测定其对肺炎克雷伯杆菌MIC,MBC,绘制杀菌曲线,并通过透射电镜研究其作用机制。结果成功合成目标化合物,通过单晶衍射分析确定为5-氯水杨醛缩2,4-二羟基苯酰肼。抗菌结果表明该化合物对肺炎克雷伯菌的MIC为1．25mg／mL,MBC为2．5mg／mL。杀菌曲线结果表明该化合物对肺炎克雷伯菌的杀菌作用表现出明显的浓度依赖性。电镜结果表明该化合物的作用机制可能与破坏菌体细胞壁,改变细胞膜通透性有关。结论产物5-氯水杨醛缩2,4-二羟基苯酰肼有较好的抗肺炎克雷伯杆菌的作用。     

萘查耳酮类化合物的设计合成及对CYP1B1酶的抑制活性评价

目的:设计并合成几类新型的萘查耳酮衍生物,初步测定其对CYP1B1酶的抑制活性,筛选具有良好抗癌作用的CYP1B1抑制剂。方法:以1,5-二羟基萘为原料,首先合成两个重要的中间体2-乙酰基-1,4,5,8-四甲氧基萘、1,5,6-三甲氧基-2-萘乙酮,然后利用羟醛缩合反应合成所需要的化合物。结果:合成了19个目标化合物,其结构均经过核磁共振氢谱确证,所有化合物均为全新化合物。对所合成的新化合物均进行了EROD酶实验测定。结论:所合成的化合物均具有较强的CYP1B1酶一抑制活性,其中4-1、4-2、5'-1对CYP1B1的抑制活性强于CYP1B1强抑制剂α-萘黄酮(IC50=11 nmol/L),他们的IC50分别为6.5、0.47、8nmol/L。     

柚皮素酰腙类衍生物的合成、体外抗氧化活性以及细胞毒性研究

柚皮素具有良好的抗氧化活性,但由于其生物利用率低,导致其应用受限。本文合成得到13种柚皮素的酰腙类衍生物,其中12种未被文献报道。采用ABTS、FRAP、DPPH 3种方法测定了合成衍生物与柚皮素的体外抗氧化活性。结果显示13种化合物的抗氧化活性均强于柚皮素,其中8种衍生物的体外抗氧化活性是柚皮素活性的3到6倍。细胞毒性实验中细胞存活率90%时,可认为化合物对细胞无抑制。8种化合物对HEK293细胞的细胞毒性实验结果显示,在0～25μmol/L浓度范围内,衍生物b、g、j、k、l对HEK293细胞存活率大于90%,其中衍生物g、k、l的浓度在0～50μmol/L时,HEK293细胞的存活率仍大于90%,而衍生物j在浓度高达100μmol/L时细胞存活率仍大于90%。研究结果为后期的抗氧化食品添加剂及抗氧化药物筛选提供理论依据。     

白藜芦醇及其水溶性衍生物的合成

目的:合成白藜芦醇及其水溶性衍生物。方法:以3,5-二甲氧基苯甲醛和4-甲氧基碘苯为原料,经Wittig反应,Heck偶联,脱甲基反应,连接侧链等合成白藜芦醇及其衍生物,并使用紫外法测定其在水中的溶解度大小。结果:目标化合物经核磁共振氢谱,质谱等确证为白藜芦醇及其水溶性衍生物,且水溶性提高3倍。结论:该方法的反应路线步骤短,操作简便,对反式产物选择性高。     

Reactions of withaferin-A with model biological nucleophiles

Withaferin-A was reacted with three model biological nucleophiles: ethyl mercaptan, thiophenol, and -cysteine ethyl ester. Under neutral or alkaline conditions, each of the thiols underwent facile Michael addition with the antitumor agent. The most chemically reactive site for Michael Addition reactions with the model thiols was the unsaturated A-ring of withaferin-A. The possible significance of this reaction with regard to antitumor activity is discussed.     

Anti-tumor and anti-leishmanial evaluations of 1,3,4-oxadiazine, pyran derivatives derived from cross-coupling reactions of β-bromo-6H-1,3,4-oxadiazine derivatives

Cyanoacetylhydrazine reacted with the ω-bromoacetophenones 2a,b to give hydrazide-hydrazone derivatives 3a,b. The latter products were cyclized to the 1,3,4-oxadiazine derivatives 4a,b. Bromination of the latter products gave the 6-bromo-6H-1,3,4-oxadiazine derivatives 5a,b which underwent a series of cross-coupling reactions. The antitumor evaluation of the newly synthesized products against the three cancer cells namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of them have high inhibitory effect towards three cell lines which is higher than the standard. Moreover, the anti-leishmanial activity of the newly synthesized product was tested on Leishmania donovani amastigotes showed that some compounds have high activity.     

Antioxidant activity and antitumor activity (in vitro) of xyloglucan selenious ester and surfated xyloglucan

Two kinds of xyloglucan derivatives (xyloglucan selenious ester and sulfated xyloglucan) were prepared and evaluated on antioxidant activity and antitumor activity. Compared with xyloglucan, xyloglucan derivatives have new bioactivity against oxidative damage and tumor. Furthermore, xyloglucan selenious ester is more potent than sulfated xyloglucan at antioxidant activity and antitumor activity in vitro. The current data suggest for the first time that selenition of xyloglucan significantly increases its bioactivity and the chemical modification of polysaccharide may allow the preparation of derivatives with new properties and a variety of applications.     

Synthesis of 1-(2-naphthylsulfonyl)pyrazole-C-glycosides

2-Naphthylsulfonylhydrazine was reacted with aromatic aldehydes or aldehydo sugars to give the corresponding hydrazones which undergo Michael addition reactions with malononitrile or ethyl cyanoacetate to form pyrazole derivatives.     

Synthesis and antitumor activity of novel C-8 ester derivatives of leinamycin

A novel series of C-8 ester derivatives of leinamycin are described. Condensation of N-substituted amino acids or carboxylic acids containing polyether moiety with leinamycin resulted in the C-8 ester derivatives with good antitumor activity in several experimental models. Among these derivatives, compound 4e, which has five ethylene glycol ether units in the C-8 acyl group, showed potent antitumor activity against human tumor xenograft. Combination with the modification of the dithiolanone moiety was applied to these C-8 ester derivatives and some of them also showed good antitumor activity.     

Synthesis and antitumor activity of bicyclo[3.3.1]nonenol derivatives

Various novel bicyclo[3.3.1.]nonenol derivatives were synthesized in an efficient one-pot procedure in a remarkably stereoselective reaction. The title compounds show significant antitumor activity against human cancer cell lines. A variety of cinnamic acid derivatives were linked to the title compounds as side chains in order to enhance the antitumor activity. These compounds were subjected to the in vitro antitumor screening, and the results are discussed. It seems important with respect to antitumor activity to locate an aromatic ring at the C-7 position of the bicyclo[3.3.1]nonane framework.     

Platinum complexes of diaminocarboxylic acids and their ethyl ester derivatives: the effect of the chelate ring size on antitumor activity and interactions with GMP and DNA

A number of new Pt(II) complexes is described having the general formula PtCl(2)(LL), where LL is a chelating diamine ligand. Ligands LL were chosen as D,L-2,3-diaminopropionic acid and its ethyl ester, and D,L-2,4-diaminobutyric acid and its ethyl ester. The compounds were characterized using analytical and spectroscopic methods. The influence of the size of the chelate ring and its functionalization on the biological properties was studied. It was demonstrated by circular dichroism (CD) that the effects on the secondary structure of DNA induced by the four complexes are different. The interaction takes place at the N7 position of the purine bases, as shown by NMR studies. The platinum complexes of 2,3-diaminopropionic acid and 2,4-diaminobutyric acid are able to form intrastrand adducts with DNA and to distort the double helix by changing the base stacking. The ethyl ester derivatives uncoil the DNA from the B form to the C form. The interactions with 5'-GMP and DNA were compared with their antitumor activity. The platinum complexes of diaminocarboxylic acids exhibit cytotoxic activity in the A431, HeLa, and HL-60 cell lines in a dose- and time-dependent manner.     

SYNTHESIS OF 1-(2-NAPHTHYLSULFONYL)PYRAZOLE-C-GLYCOSIDES

ABSTRACT

2-Naphthylsulfonylhydrazine was reacted with aromatic aldehydes or aldehydo sugars to give the corresponding hydrazones which undergo Michael addition reactions with malononitrile or ethyl cyanoacetate to form pyrazole derivatives.     

Amide and ester derivatives of N3-(4-methoxyfumaroyl)-(S)-2,3-diaminopropanoic acid: the selective inhibitor of glucosamine-6-phosphate synthase

Several amide and ester derivatives of a glutamine analogue, N3-(4-methoxyfumaroyl)-(S)-2,3-diaminopropanoic acid (FMDP) (1-8), were synthesized and evaluated for the inhibitory activity in regard to glucosamine-6-phosphate synthase from Candida albicans. The syntheses were accomplished by the reaction of N2-tert-butoxycarbonyl-N3-(4-methoxyfumaroyl)-(S)-2,3-diaminopropanoic acid (BocFMDP) with the corresponding amines to give the FMDP amides (1-4) or with alkyl halides to give corresponding esters of FMDP (5-8). Among the synthesized compounds, the acetoxymethyl ester of FMDP was the most active inhibitor of the enzyme. Its IC50 value compared to that of FMDP (4 microM) was equal to 11.5 microM. The methyl and allyl esters and the N-hexyl-N-methyl-amide of FMDP exhibited a moderate enzyme inhibitory activity.     

Synthesis and cytotoxic activity of novel C7-functionalized spongiane diterpenes

Based on two lead cytotoxic spongiane diterpenes, a new series of C7-oxygenated derivatives were synthesized and evaluated for their antitumor activity in vitro against the cancer cell lines HeLa and HEp-2. In general, introduction of either hydroxyl or acetoxy groups at C-7 did not improve the resultant cytotoxicity, while the presence of a butyrate ester led to more active compounds (CC(50)=4.0-9.5 microM).