新型取代查尔酮-哌嗪衍生物的合成及其生物活性评价（英文）

为了寻找结构新颖的活性分子,采用活性亚结构拼接的方法,设计合成了24个未见文献报道的取代查尔酮-哌嗪衍生物,其结构经~1H NMR、~(13)C NMR和HRMS确证.分别采用小鼠巨噬细胞Raw 264.7炎症模型和噻唑蓝(MTT)法对目标化合物的体外抗炎活性和细胞毒活性进行测试,结果表明,查尔酮母核和哌嗪环上的取代基对化合物的生物活性有明显影响.特别是3,4,5-三甲氧基-4'-[N-(2-氧代丙基)-1-哌嗪基]查尔酮(11)能有效抑制NO的生成(IC50=3.81μmol/L),4-溴-4'-[N-(4'-甲基-2-氧代苯乙基)-1-哌嗪基]查尔酮(25)对三种肿瘤细胞株(Hela,A549和sk-ov-3)均表现出良好的体外细胞毒活性(IC50值分别为0.54,0.05和9.12μmol/L).     

含N-取代哌嗪片段的查尔酮衍生物的合成及其细胞毒活性

以4-甲氧基苯甲醛与2-溴-4’-氟苯乙酮为原料,经缩合、取代反应后,再与α-溴代酮或α-溴代酯反应,合成得到8个查尔酮哌嗪衍生物(3a~3h),其结构经1H NMR、13C NMR和HRMS确证。采用MTT法初步测试了所合成化合物的体外细胞毒活性,结果表明,哌嗪环上含酮基取代的化合物对肿瘤细胞株A549和SGC7901均表现出良好的抑制活性,特别是化合物3a(IC50=0.28μmol/L,2.53μmol/L)活性最高,值得进一步深入研究。     

含酰基哌嗪片段的呋喃查尔酮衍生物的合成及其抗炎活性研究

依据活性结构单元的拼合原理,以2-呋喃甲醛和4-氟苯乙酮为原料出发,经Aldol缩合、脱水、哌嗪取代反应生成4’-(1-哌嗪基)呋喃查尔酮(2)后,再与酰氯和磺酰氯反应,得到了10个未见报道的含哌嗪取代的呋喃查尔酮衍生物,其结构经~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw 264.7模型初步测试了目标化合物的体外抗炎活性,结果表明,磺酰胺类化合物的抗炎活性要优于酰胺类化合物,特别是化合物4d能有效抑制NO的生成(IC_(50)=3.88μmol/L),与阳性对照药地塞米松活性相当。     

新型白藜芦醇-查尔酮酰胺衍生物的合成及其细胞毒活性（英文）

白藜芦醇又名芪三酚,是一种生物活性很强的茋类化合物.在前期研究基础上,采用活性亚结构拼接的方法,将白藜芦醇与查耳酮片段连接起来,以寻找活性较高的新型抗肿瘤分子.白藜芦醇经Vilsmeier甲酰化、Aldol缩合、哌嗪取代及酰胺化反应,设计合成了13个未见文献报道的白藜芦醇-查尔酮衍生物,其结构经IR、~1H NMR、~(13)C NMR和HRMS确证.采用噻唑蓝(MTT)法对目标化合物的体外细胞毒活性进行测试,结果表明,该类化合物具有较强的体外细胞毒活性,特别是(E)-3-(2,4-二甲氧基-6-((E)-4-甲氧基苯乙烯基)苯基-1-(4-(N-丙烯酰基)哌嗪-1-基)苯基丙烷-2-烯-1-酮(9)对肿瘤细胞株(A549和Hela)均表现出良好的体外细胞毒活性(IC_(50)值分别为0.26和7.35μmol·L~(-1)).并且,流式细胞技术分析表明化合物9能够显著诱导肿瘤细胞A549的凋亡.     

新型4'-(N-取代-1-哌嗪基)查尔酮衍生物的合成及其抗肿瘤活性

为了寻找活性较高的抗肿瘤新型分子,采用活性亚结构拼接的方法,将查尔酮和哌嗪连接起来,并通过衍生化,设计合成了10个未见文献报道的新型4'-(N-取代-1-哌嗪基)查尔酮衍生物3a~3j,其结构经~1H NMR、~(13)C NMR和HRMS确证.采用溴化噻唑蓝四氮唑(MTT)法测试了目标化合物体外抗肿瘤活性(Hela,A549和SGC7901),结果表明化合物3f、3i和3j均表现出良好的细胞毒活性,可做进一步研究.     

新型N-杂环取代查尔酮衍生物的合成

以4-二甲氨基苯甲醛与4'-氟苯乙酮为原料,经羟醛缩合反应制得4-二甲氨基-4'-氟查尔酮(1);1分别与咪唑、哌嗪等含氮杂环化合物经取代反应合成了6个新型的N-杂环取代查尔酮衍生物,其结构经1H NMR,13C NMR和IR表征。     

新型查尔酮哌嗪衍生物的合成

以4-二甲氨基苯甲醛和2-溴-4′-氟苯乙酮为原料,经缩合和取代反应制得4-二甲氨基-4′-(1-哌嗪基)查尔酮(2); 2与卤代烃反应合成了6个新型的查尔酮哌嗪衍生物,收率71%~88%,其结构经¹H NMR,¹³C NMR和HR-MS表征。     

3-芳基-5-噻吩基二氢吡唑磺酰胺衍生物的合成及其抗炎活性研究

二氢吡唑是一类含有多种生物活性的五元氮杂环化合物,广泛存在于各种活性天然产物结构中。本文由4-氟苯乙酮和N-甲基哌嗪经取代反应后,再与2-噻吩甲醛发生羟醛缩合生成哌嗪取代噻吩查尔酮(2)。化合物2与水合肼环化得到中间体化合物3,最后经磺酰氯衍生化,合成得到8个未见报道的3-芳基-5-噻吩基二氢吡唑磺胺衍生物(4a～4h),其结构均经IR、~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw264. 7模型初步测试了衍生物的抗炎活性,结果表明,化合物4a、4e和4h具有潜在的体外抗炎活性,特别是化合物4a抑制NO生成的IC_(50)值为12. 64μmol/L,与阳性对照药地塞米松活性相当。     

两个天然查尔酮苷的全合成

以香草酮和对羟基苯甲醛为原料,经酚羟基保护、羟醛缩合、相转移催化法接糖、去保护基等反应合成了两个天然查尔酮苷——4’-O-β-D-喃葡萄基-3’-甲氧基-4-甲氧基-查尔酮和4’-O-β-D-喃葡萄基-3’-甲氧基-4-羟基-查尔酮,总收率分别为17.2%和20.8%,其结构经1H NMR,13C NMR和HR-MS确证。在脱保护基反应中,首次提出了NH4Cl脱除MOM保护基的新方法。     

3-芳基-5-噻吩基二氢吡唑磺酰胺衍生物的合成及其抗炎活性研究

二氢吡唑是一类含有多种生物活性的五元氮杂环化合物,广泛存在于各种活性天然产物结构中。本文由4-氟苯乙酮和N-甲基哌嗪经取代反应后,再与2-噻吩甲醛发生羟醛缩合生成哌嗪取代噻吩查尔酮(2)。化合物2与水合肼环化得到中间体化合物3,最后经磺酰氯衍生化,合成得到8个未见报道的3-芳基-5-噻吩基二氢吡唑磺胺衍生物(4a～4h),其结构均经IR、~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw264. 7模型初步测试了衍生物的抗炎活性,结果表明,化合物4a、4e和4h具有潜在的体外抗炎活性,特别是化合物4a抑制NO生成的IC_(50)值为12. 64μmol/L,与阳性对照药地塞米松活性相当。     

Synthesis and Antitumor Activity Evaluation of Pyrimidine Analogues Bearing Urea Moiety

A series of 4‐anilino‐6‐phenylpyrimidines containing urea moiety were synthesized and the structures of all products were confirmed by ¹H NMR, ¹³C NMR and HRMS. The antiproliferative activities of these compounds were evaluated against three human tumor cell lines (MGC‐803, MCF‐7 and EC‐109) by applying the MTT assay method. compounds 4a , 4b and 6a showed the most effective activity, among which, 6a was more cytotoxic than 5‐fluorouracil against all tested human cancer cell lines with IC₅₀ values ranging from 1.80 to 2.72 µmol·L^?1.     

新型四氢苯并[4',5']噻吩并[3',2'∶5,6]吡啶并[4,3-d]嘧啶类化合物衍生物的合成及抗肿瘤活性

本文以环己酮为原料,通过氮杂Wittig反应合成了一系列结构新颖的取代四氢苯并噻吩并吡啶并嘧啶衍生物,并采用MTT法考察所合成目标化合物对CNE2、KB、MGC-803、MCF-7和PC3这5种肿瘤细胞的抑制活性。初步的生物活性结果表明,目标化合物对5种肿瘤细胞均有抑制活性,尤其是对胃癌MGC-803细胞展现出了更强的抑制活性。其中3-(4-氟苯基)-2-((4-氟苯基)氨基)-5-甲基-8,9,10,11-四氢苯并[4',5']噻吩并[3',2':5,6]吡啶并[4,3-d]嘧啶-4(3H)-酮[化合物8c,IC_(50)=(0. 9±0. 25)μmol·L~(-1)]对MGC-803的活性最强,是5-氟尿嘧啶[IC_(50)=(18. 4±1. 43)μmol·L~(-1)]的20倍;同时,目标化合物对正常的胃黏膜上皮细胞GES-1没有毒性。四氢苯并[4',5']噻吩并[3',2':5,6]吡啶并[4,3-d]嘧啶类化合物具有良好的抗肿瘤活性,值得进一步深入研究。     

Synthesis,characterization and catalytic,cytotoxic and antimicrobial activities of two novel cyclotriphosphazene‐based multisite ligands and their Ru(II) complexes

Two novel cyclotriphosphazene ligands ( 2 and 3 ) bearing 3‐oxypyridine groups and their corresponding Ru(II) complexes ( 4 and 5 ) were synthesized and their structures were characterized using Fourier transform infrared, ¹H NMR and ³¹P NMR spectroscopic data and elemental analysis. The Ru(II) complexes were used as catalysts for catalytic transfer hydrogenation of p‐substituted acetophenone derivatives in the presence of KOH. Additionally, the cytotoxic activities of compounds 2 , 3 , 4 , 5 were evaluated against PC3 (human prostate cancer), DLD‐1 (human colorectal cancer), HeLa (human cervical cancer) and PNT1A (normal human prostate) cell lines. Finally the antimicrobial activities of compounds 2 , 3 , 4 , 5 were evaluated against a panel of Gram‐positive and Gram‐negative bacteria and yeast cultures. The complexes showed efficient catalytic activity towards transfer hydrogenation of acetophenone derivatives, especially those bearing electron‐withdrawing substituents on the para‐position of the aryl ring. The compounds were found to have moderate to high cytotoxic and antimicrobial activities, and Ru(II) complexation enhanced both cytotoxic and antimicrobial activities in comparison with the parent compounds. Copyright © 2015 John Wiley & Sons, Ltd.     

双-β-咔啉衍生物的设计、合成及抗肿瘤活性

以去氢骆驼蓬碱为原料, 经过脱甲基、 烷基化等步骤, 合成了一系列双-β-咔啉衍生物. 目标化合物均经核磁共振谱(NMR)和质谱(MS)进行结构确证. 以顺铂为阳性对照药, 采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Bel-7402, 786-0, BGC-823, A375, 769-P和MCF7等6株细胞)活性. 结果表明, 化合物4g和4o与阳性对照药相比具有良好的抗肿瘤活性, 其半抑制浓度(IC₅₀)值均小于10 μmol/L. 初步构效关系研究表明, 当桥链亚甲基数目为8~10, β-咔啉环上9-丁基或9-异丁基取代时, 化合物的抗肿瘤活性较强.     

Design,synthesis of (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐ substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐dione analogues as potential cytotoxic agents

In an attempt to achieve promising cytotoxic agents, a series of new (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐diones 10 a‐n were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, IR, and ESI‐MS techniques. These compounds synthesized from appropriate reaction procedures with better yields. All the novel synthesized compounds 10a‐n were evaluated for their cytotoxic activity against the MCF‐7 cell line (Human breast cancer cell line) at different concentrations of 0.625, 1.25, 2.5, 5, and 10 μM, respectively. The cytotoxic evaluation assay is presented in terms of IC₅₀ values and percentage cell viability reduction compared against standard drug cisplatin. Among all novel synthesized compounds 10a‐n , some of the representative analogues particularly 10g and 10e exhibit remarkable cytotoxic activity with IC₅₀ values 0.454 and 0.586 μM, comparable to that of the standard drug cisplatin, and some analogues 10d , 10f , 10k, and 10m also have shown significant activity.     

Design,synthesis of novel quinazolin-4-one derivatives and biological evaluation against human MCF-7 breast cancer cell line

A new series of 6,8-dibromo-2-(4-chlorophenyl)quinazolin-4(3H)-one derivatives VI–XIII were synthesized. Their chemical structures were confirmed by spectral and elemental analysis. The cytotoxic effect of the newly synthesized compounds was tested in vitro against human breast cancer cell line (MCF-7). Most of the tested compounds have shown promising cytotoxic activity. Compounds X and XIIIb exerted a powerful cytotoxic effect against MCF-7 with a very low IC50 (0.0015 and 0.0047 µmol/ml), while compounds VI, VII, VIII, XIIb, XI, XIIIc and IX exerted a moderate cytotoxic effect (IC50 0.01523, 0.0213, 0.031, 0.0478, 0.049, 0.068 and 0.079 µmol/ml respectively), compared to doxorubicin (0.0025 µmol/ml). Exploring their apoptotic effect; interestingly,all compounds activated apoptotic cascade in MCF-7. Compounds VI, XIIIb, XIIb, XI, XIIa, VII, V and VIII showed potent effect even much more than doxorubicin by 12.87–5.91 folds, while compounds XIIIc, IX, XIIIa, XIIc and X showed moderate increase in CASP3 activity by 4.96–3.22 folds relative to untreated cells more or less similar to doxorubicin (5.57 folds).     

2-(2’,6’-二氯苯基)-1,3-噻唑烷-4-酮衍生物的微波促进合成及抗真菌、 抗肿瘤活性研究

利用微波促进的方法, 以2,6-二氯苯甲醛、胺和巯基乙酸为原料, 合成了系列N-3位不同取代基团的噻唑烷酮衍生物. 部分化合物在Lawesson试剂作用下, 合成了其系列噻唑烷4-硫酮衍生物. 所有化合物通过IR, 1H NMR, MS和元素分析等方法确定结构. 测试了化合物对黄瓜白粉病菌的抑制活性和对宫颈癌细胞的毒性作用, 部分化合物表现出较好的生物活性.     

Metal‐based sulfonamides: synthesis,characterization, antibacterial,antifungal and cytotoxic properties of pyrrolyl‐ and thienyl‐derived compounds

Pyrrolyl and thienyl derived sulfonamides and their metal [cobalt(II), copper(II), nickel(II) and zinc(II)] complexes were synthesized and characterized by elemental analyses, molar conductances, magnetic moments, IR, ¹H NMR, ¹³C NMR and electronic spectral data. These compounds were screened for in‐vitro antibacterial activity against four Gram‐negative (Escherichia coli, Shigella flexeneri, Pseudomonas aeruginosa and Salmonella typhi) and two Gram‐positive (Bacillus subtilis and Staphylococcus aureus) bacterial strains, and for in‐vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. The results of these studies revealed that all compounds showed significant to moderate antibacterial activity; however, the zinc complexes were shown to be the most active against various species. The brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties of all the synthesized ligands and their metal complexes. Only two compounds ( 14 and 19 ) displayed potent cytotoxic activity as LD₅₀ = 5.5637 × 10^?4 and 4.4023 × 10^?4 M ml^?1 respectively, against Artemia salina. Copyright © 2007 John Wiley & Sons, Ltd.     

Design,synthesis, and antimicrobial evaluation of some nifuroxazide analogs against nosocomial infection

A series of 10 p-substitutedbenzoylmethylene hydrazide derivatives 4a-j were synthesized by protecting carboxylic group of 4-hydroxybenzoic acid using methanol and sulfuric acid than reacting it with hydrazide to form 4-hydroxybenzohydrazide followed by reacting with a variety of aldehydes and evaluated for their activity against nosocomial infection. All the synthesized compounds were characterized by Fourier-transform infrared (FT-IR), ¹H nuclear magnetic resonance (NMR), and mass spectral data. The in vitro antimicrobial potential of synthesized compounds was estimated against prominent strains of nosocomial pathogens (Staphylococcus aureus, Escherichia coli, and Aspergillus niger). The antimicrobial evaluation revealed compounds 4b , 4c , 4d , 4e , 4f , and 4j to be the most active compounds of the series with IC₅₀ value for antibacterial in the range 0.39 to 0.75 μM/mL. Furthermore, the in vitro cytotoxic potential of the compounds was appraised by hemolytic assay. The results showed that some of the synthesized compounds exhibited marked activity.     

Antiproliferative,Cytotoxic, and Apoptotic Effects of New Benzimidazole Derivatives Bearing Hydrazone Moiety

In order to take the advantages of the anticancer properties of benzimidazoles and hydrazones, we synthesized new 4‐(5‐chloro‐1H‐benzimidazol‐2‐yl)‐benzoic acid benzylidene hydrazide derivatives ( 3a–3t ) and evaluated their anticancer activity against A549 (human lung adenocarcinoma) and MCF‐7 (human breast adenocarcinoma) cells. The structures of the compounds ( 3a–3t ) were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, mass spectroscopy, and elemental analyses. Antiproliferative activities of the compounds were evaluated using MTT assay, BrdU method, and flow cytometric analysis. In addition, with purpose of determining selectivity the cytotoxic activities of the final compounds were screened against healthy NIH3T3 cell line (mouse vembryonic fibroblast cells). Among the tested compounds 3e and 3f showed significant cytotoxic activity against A549 and MCF‐7 cancer cells with an IC₅₀ value of 0.0316 μM. Furthermore, compound 3p showed remarkable cytotoxic activity against MCF‐7 comparing with standard drug cisplatin. Annexin V‐FITC assay also suggested that this compounds induced cell death by apoptosis.