Design,synthesis and biological evaluation of E-ring modified evodiamine derivatives as novel antitumor agents

A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase Ⅰ and Ⅱ was evaluated by the relaxation assay. In vitro antitumor activity results revealed that compound 12 showed good antitumor activity with a broad spectrum. Its binding modes with topoisomerase Ⅰ and Ⅱ were clarified by molecular docking.     

吲哚马来酰亚胺类化合物的合成及其抗肿瘤活性

为寻找具有抗肿瘤活性的新化合物, 设计合成吲哚马来酰亚胺类化合物, 并评价其体外抗肿瘤活性. 以吲哚与2-氯乙酰胺为起始原料, 经取代、缩合等反应合成了单吲哚马来酰亚胺衍生物5a～5t, 以5-硝基吲哚和不同的N-(3-氯丙基)叔胺经取代、还原、缩合等反应得到了双吲哚马来酰亚胺衍生物9a～9f. 共合成了26个未见文献报道的新化合物, 其结构经质谱、元素分析和核磁共振氢谱确证. 采用MTT法, 测试了目标化合物对肿瘤细胞株HL60, ECA-109, A549, SMMC-7721和PC-3的增殖抑制活性, 结果表明部分化合物对所测肿瘤细胞株均显示一定的抑制作用.     

主链含酪氨酸的聚磷酸酯抗肿瘤药物的研究

通过含酪氨酸的聚磷酸酯与药物分子进行大分子反应，制备了含５－氟尿嘧啶或氨甲蝶呤的聚磷酸酯。所得聚磷酸酯均具有两亲性，部分聚磷酸酯在水中能形成胶束。研究了这些聚合物的体外降解和释药性能，体外抗肿瘤实验表明，有些聚磷酸酯药物具有较强的抗肿瘤活性。     

Chemical Synthesis and In Vitro Antitumor Activity of Quinizarin Glycoside Analogs

A series of new glycoside derivatives of quinizarin were synthesized and characterized by NMR and IR spectrometry, and in vitro antitumor activity of some of these derivatives was evaluated against the mouse leukaemia P388 and the human leukaemia HL-60 cell lines by the standard MTT assay. They were proven to possess moderate antitumor activity.     

含己烷雌酚的聚磷酸酯的合成及其抗肿瘤活性研究

合成了３种主链含己烷雌酚的生物可降解的聚磷酸酯，结构经ＩＲ，＾１ＨＮＭＲ和元素分析鉴定，通过水接触角的测定研究了聚合物的亲水－疏水性能，以ｐＨ值变化表征了聚合物的体外水解速率。初步的体外实验表明，此类聚磷酸酯具有较好的体外抗艾氏腹水癌活性。     

Synthesis and Antitumor Activity of 7-Substituted Derivatives of Homocamptothecin

Camptotecin is the parent of an important class of anticancer agents which, can selectively poison the ubiquitous nuclear enzyme topoisomerase. Water soluble camptothecin analogues such as topotecan and irinotecan are already approved for clinical uses in…     

Synthesis and antitumor activity of novel 10-amino acids ester homocamptothecin analogues

Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method. The results showed that some of the compound had higher antitumor activity than iritecan.     

Analysis of antitumor active OSW-1 and its analogues by liquid chromatography coupled with electrospray and atmospheric pressure chemical ionization quadrupole mass spectrometry

Three cholestane glycosides including OSW-1 with antitumor activity and two new analogues with modified steroidal side chains, thienyl OSW-1 and silylated thienyl OSW-1, were synthesized. Analyses were performed using optimized, reversed-phase liquid chromatography (LC) with electrospray ionization and atmospheric pressure chemical ionization quadrupole mass spectrometry (MS). The ionization mode and polarity, cone voltage, and chromatographic conditions were evaluated. The optimum LC/MS conditions to obtain valuable ions, indispensable for identifying the structures, are described. The key fragmentation pathways, which will be useful for confirming the detailed structures of steroidal glycosides, are also proposed.     

Synthesis and anti-tumor activity of new steroidal nuclear analogues of aragusterol A

3alpha,7alpha-Dihydroxy-5-epiaragusterol A (3) was synthesized from bile acid (cholic acid) as a new steroidal nuclear analogue of antitumor marine steroid aragusterol A. 7alpha-Hydroxyaragusterol A (4) was also derived from xestokerol B. The in vitro anti-proliferative activity of each of these analogues toward KB cells as well as in vivo anti-tumor activity of 5-epiaragusterol A (2) previously synthesized by the authors and 3 were assessed.     

Chemical Synthesis of Several 2'-O-, 3'-O-Glycosylated Diosgenyl β-D-Glucopyranosides

ABSTRACT

Six 2'-O-, 3'-O-glycosylated diosgenyl β-D-glucopyranosides (4-9), which have a typical structural pattern of diosgenyl saponins, were synthesized; their synthetic routes are discussed.     

Synthesis and antitumor activity of 7-azaindirubin

Twenty 7-azaindirubin derivatives were designed and synthesized.Their antitumor activities were evaluated in vitro against DU145 cell line.The pharmacological results showed that most of the prepared compounds displayed the excellent activity.Compound 18 exhibited the most potent antitumor activity among the tested compounds.     

Facile synthesis and cytotoxicity of 5-C-alkylates of 20（S）- camptothecins

A series of 5-C-alkylating camptothecins have been synthesized by one-step method, and their in vitro antitumor activity was evaluated against six human cancer cell lines. The results showed that all 5-C-alkylates of camptothecins possessed poor cytotoxicity on six human cancer cell lines.     

Molecular docking and biological assessment of substituted phthalazin-1(2H)-one derivatives

2, 4-Disubstituted phthalazin-1(2H)-one derivatives were synthesized via nucleophilic attack of N-2 of phthalazin-1(2H)-one derivatives on different alkyl halides. In addition, reactive phthalazinone acetohydrazide derivative was utilized as a scaffold to synthesize different heterocyclic systems. The assigned structures for all the newly synthesized derivatives were confirmed on the basis of elemental analyses and spectral data. Mechanistic illustrations for some of the synthesized compounds were also discussed. The synthesized compounds were evaluated for in vitro antimicrobial and antitumor activity. Most of the tested compounds exhibited significant potency as antimicrobial and antitumor agents. Moreover, MOE 2014.09 software was utilized to carry out computational studies to support the biological activity results.     

A Novel 5-Fluorouracil Salt of 12-Silicatungstic Acid： Synthesis, Structure Characterization and Antitumor Activity

A novel 5-fluorouracil salt of 12-silicatungstic acid was synthesized and characterized by means of elemental analysis, IR,^1H NMR and ^183W NMR spectra. The antitumor activity and toxicity of the complex have been evaluated both in vitro and in vivo.     

N-(4-哌啶基)苯甲酰胺衍生物的设计、合成及其抗肝癌活性

以4-羟基苯甲酸乙酯为原料,经烃化、水解、缩合、脱保护、磺酰化反应,合成了6个含有磺酰基取代的4-苯氧基-N-(4-哌啶基)苯甲酰胺衍生物。 其结构经¹H NMR、¹³C NMR和MS谱等技术手段进行了表征,并以索拉非尼为阳性对照药对HepG2细胞株进行了初步体外抗肝癌细胞增殖活性的评价。 实验发现,4-苯氧基-N-(1-甲磺酰基哌啶-4-基)苯甲酰胺的体外抗肝癌生物活性优于索拉非尼,IC₅₀值为8.42 μmol/L。 研究结果表明,新结构4-苯氧基-N-(4-哌啶基)苯甲酰胺类化合物具有良好的抗肝癌活性。     

氟喹诺酮C-3均三唑硫醚酮缩氨基硫脲衍生物的合成及抗肿瘤活性

为发现氟喹诺酮由抗菌活性向抗肿瘤活性转化的结构修饰方法,基于生物电子等排药物设计原理,用唑杂环作为氧氟沙星(1)C-3羧基的等排体、硫醚酮缩氨基硫脲为其功能侧链修饰基,设计合成C-3均三唑硫醚酮缩氨基硫脲目标化合物(6a~6g),其结构经元素分析和光谱数据确证。 体外抗肿瘤活性结果表明,中间体C-3均三唑硫醚酮(5a~5g)和目标化合物(6a~6g)的活性均强于母体氧氟沙星的活性,其中缩氨基硫脲的活性强于相应硫醚酮的活性,尤其是苯环含硝基和氟原子目标化合物的活性与对照药阿霉素的活性相当。 因此,功能缩氨基硫脲链修饰的均三唑作为C-3羧基的等排体有利于提高氟喹诺酮的抗肿瘤活性。     

Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. III. Synthesis and antitumor activity of 3-phenylpiperazinyl-1-trans-propenes

A series of novel 3-[4-phenyl-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes and related compounds were synthesized and evaluated by their cytotoxic activity against several tumor cell lines in vitro and in vivo antitumor activity against some tumor models when administered both intraperitoneally and orally. Compounds with the 3-chloropyridin-2-yl group (9g) and the 3-fluoro-5-substituted phenylpiperazinyl group (29b, c, and e) showed significantly potent cytotoxicity by in vitro testing. Among them, the 3-cyano-5-fluorophenyl derivative (29b) exhibited potent antitumor activity against several tumor cells including human carcinoma without causing undesirable effects in mice.     

新型N-甲基吲哚类衍生物的设计、合成及抗肿瘤活性研究

本文以吲哚骨架为起点,设计合成了5个含吲哚骨架的新型有机小分子(4a-4e),通过NMR,IR和MS对目标化合物进行了结构表征.采用MTS法测试了目标化合物对SMMC-7721,Hela,MCF-7和HepG2癌细胞的体外抗肿瘤活性.结果表明,部分化合物选择性地作用于一种细胞,显示出较强的抑制肿瘤细胞增殖的活性,值得进一步研究.     

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 Characterization of Novel Azo-containing or Azoxy-containing Schiff Bases and Their Antiproliferative and Cytotoxic Activities

A series of novel Schiff base derivatives was designed and synthesized from 3,3'-azobenzaldehyde and 3,3'-azoxybenzaldehyde. The newly synthesized compounds were characterized by FTIR, ¹H NMR, MS and elemental analysis and tested for their in vitro antiproliferative activities against HeLa cell lines. At the same time, the impact on the antitumor activity of the sulfanilamido, benzamido, phenolic hydroxyl or thiourea groups was investigated and discussed. Compounds 4, 6 and 10 were found to exhibit strong cytotoxic activity.