用三种不同方法研究TPPS4与DM-β-CD的相互作用

本文以极谱法、荧光光谱法和紫外可见光谱法研究了水溶性卟啉四-(4-磺基苯)卟啉(TPPS4)与2,6-二-氧-甲基--βCD(DM--βCD)的相互作用。结果表明,二者可发生反应,形成了TPPS4-DM--βCD的超分子体系。此外,本文还用极谱法和紫外-可见光谱法对TPPS4-DM--βCD超分子体系的包结比和包结常数进行测定,证明二者形成了1∶2的包结物;计算所得的包结常数为1.44×108L2.mol-2。     

含苯并呋喃结构的咪唑盐的合成及体外抗肿瘤活性的研究

水杨醛与2-溴-4'-氟苯乙酮经过取代、缩合反应后,与咪唑取代生成2-(4-咪唑基苯甲酰基)苯并呋喃2,再与不同卤代烃反应,合成7个新的苯并呋喃类咪唑盐(3a-3g),并采用IR、1H NMR、13C NMR和HRMS对化合物的结构进行了表征;采用MTT法初步测试了目标化合物体外抗肿瘤(Hela,A549和H1975)活性,结果表明化合物3a对Hela,A549和H1975均表现出较好的抑制活性(IC5021μM)。     

呫吨酮并吡啶季铵盐的合成及其生物活性

以邻碘苯甲酸和8-羟基喹啉为原料,通过Ullmann反应合成了呫吨酮并吡啶(2),再将其进行季铵化反应合成了它的甲基及乙基季铵盐化合物3a和3b,用IR、NMR、MS及元素分析等测试技术对其结构进行了表征。运用四甲基偶氮唑盐微量酸反应比色法(MTT法)测得化合物3a和3b对体外培养人卵巢癌(A2780)、宫颈癌(Hela)、肺癌(SPC-A)和口腔上皮癌(KB)细胞的抑制作用均优于阳性对照药5-氟尿嘧啶(5-Fu)。溴乙锭置换荧光探针法测得化合物3a和3b与小牛胸腺DNA(CT-DNA)的表观结合常数分别为3.91×105和2.72×105L/mol,揭示目标化合物的抗癌活性可能与其跟DNA的相互作用有关。化合物3a和3b对乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BuChE)均具有良好的选择性抑制活性,IC50值达μmol/L以下,与阳性对照药氢溴酸加兰他敏(Galantamine.HBr)近似,它们对AChE的抑制作用为非竞争性抑制。     

席夫碱Zn(Ⅱ)配合物的合成及体外抗肿瘤活性

合成了2-吡啶甲醛缩苯二胺双席夫碱Zn(Ⅱ)配合物,通过元素分析和IR对配合物进行了表征。采用MTT法评价配合物体外抗肿瘤细胞增殖活性,通过光谱法和粘度测定法研究生理pH条件下Zn(Ⅱ)配合物与DNA的相互作用。结果表明,2-吡啶甲醛缩苯二胺双席夫碱Zn(Ⅱ)配合物对人白血病细胞(K-562)、人肝癌细胞(SMMC-7721)、人乳腺癌细胞(MCF-7)均有较强的体外抗肿瘤细胞增殖活性,配合物以部分插入方式与DNA结合。     

吖啶-多胺类缀合物的合成、 抗肿瘤活性及与DNA键合作用

设计合成了系列吖啶-多胺类衍生物(ACP1~ACP6), 并通过四甲基偶氮唑蓝(MTT)染色法研究了化合物对K562(人白血病细胞)、 A549(人肺癌细胞)和Hela(人宫颈癌细胞)细胞株的体外抗肿瘤活性. 结果显示, 化合物对肿瘤细胞具有一定的抑制作用, 尤其是化合物ACP2的抗肿瘤活性优于阳性对照顺铂. 通过UV-Vis光谱、 荧光光谱、 圆二色谱和热变性实验研究了合成化合物与小牛胸腺DNA(Ct-DNA)的键合作用. 结果表明, 三乙烯四胺修饰的化合物ACP2具有较好的抗肿瘤活性, 与DNA分子具有较强的结合能力.     

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.     

聚乙烯胺类修饰萘酰亚胺衍生物的合成、DNA键合行为和活性研究

合成了二乙烯三胺、三乙烯四胺和四乙烯五胺等低分子量聚乙烯胺类修饰的萘酰亚胺衍生物.通过UV-Vis谱、荧光光谱、圆二色谱和热变性试验研究了合成化合物与小牛胸腺DNA的键合行为,同时通过四甲基偶氮唑蓝(MTT)染色法研究了化合物对Bel-7402(人肝癌细胞)、HL-60(白血病细胞)、A549(人肺癌细胞)和Hela(人宫颈癌细胞)等细胞株的体外抗肿瘤活性,化合物NI1对A549细胞显示良好的抑制活性,优于阳性对照顺铂.     

17-(2′,5′-二取代噁唑基)-雄甾-4,16-二烯-3-酮的合成及抗肿瘤活性研究

以4-雄烯二酮1为原料,用金催化甾炔法设计并合成了一系列17-(2′,5′-二取代噁唑基)-雄甾-4,16-二烯-3-酮衍生物4a~4k.所合成产物通过1H NMR,13C NMR,IR和HRMS方法进行了结构表征.以阿比特龙为阳性对照,通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法测试了目标化合物对MCF-7(人乳腺癌细胞)、A549(人肺癌细胞)、Bel-7402(人肝癌细胞)、Hela(人宫颈癌细胞)和PC-3M-1E8(人前列腺癌细胞)的体外抗肿瘤活性.结果表明大多数化合物表现出了较好的抗肿瘤活性,其中化合物4c,4g,4i和4j的抗肿瘤活性与阳性对照物阿比特龙相当,且所测化合物对MCF-7有较好选择性作用,其IC50值在3.0~25.5μmol/L之间.     

2-取代苯氨基喹唑啉衍生物的合成及抗肿瘤活性研究

以2,4-喹唑啉二酮为起始原料,通过氯代、Suzuki偶联和芳环亲核取代反应得到一系列2-取代苯氨基喹唑啉衍生物,并经~1H NMR,~(13)C NMR和HRMS进行结构确证.应用溴化噻唑蓝四氮唑(MTT)法对目标化合物进行了初步体外抗肿瘤细胞增殖活性研究.结果表明,部分化合物具有较好的体外抗肿瘤细胞增殖活性,其中活性化合物4u和4v对Hela,A549和MCF-7三种肿瘤细胞株的增殖均有明显抑制作用.     

N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺的合成与抗肿瘤活性

采用衍生法,在N-[4-叔丁基-5-(4-氯苄基)噻唑-2-基]脂肪酰胺酰基的α-位,插入氨基,设计合成了N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺衍生物.以4,4-二甲基-1-芳基-3-戊酮为原料,经4-叔丁基-5-苄基-2-氨基噻唑(3),再经氯乙酰化和取代反应得21个N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺(1),其结构经~1H NMR、~(13)C NMR和元素分析确证.噻唑蓝(MTT)法体外抗肿瘤活性测试表明,该类新化合物对肺癌细胞(A549)、宫颈癌细胞(Hela)和乳腺癌细胞(MCF-7)具有抗肿瘤活性.其中N-[4-叔丁基-5-(胡椒基)噻唑-2-基]吗啉基乙酰胺(1t)对Hela细胞的抑制活性最好;对优选化合物1t进行了AO/EB双染和细胞周期实验,流式细胞仪分析表明,化合物1t可显著诱导肿瘤细胞凋亡,阻滞Hela细胞有丝分裂在S期.     

Synthesis and Cytotoxicity Evaluation of Novel Andrographolide‐1,2,3‐Triazole Derivatives

A series of new andrographolide‐1,2,3‐triazole derivatives, 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , were synthesized from a natural bioactive labdane type diterpenoid, andrographolide. All the derivatives were screened against human cancer cell lines MCF7, MDA‐MB‐231, COLO205, HepG2, K562, Hela, and HEK293 to evaluate their cytotoxic activity. All the compounds showed anticancer activity selectively against K562 cell line, with IC₅₀ values ranging from 8.00 to 17.11 µM, and are inactive against the rest of the cell lines. Compounds 3c and 3d showed significant cytotoxicity among the synthesized derivatives. The in silico docking studies revealed compounds 3b and 3d with high binding affinity against the cancer target, transient receptor potential vanilloid 1.     

Metal‐based antitumor,cytotoxic and antimicrobial activity: pharmacological evaluation of Knoevenagel condensate β‐diketone Schiff base thiosemicarbazone Cu(II) and Zn(II) complexes

Knoevenagel condensate Schiff base ligands [L = 3‐cinnamalideneacetylacetone‐thiosemicarbazone (CAT)/3‐cinnama‐ lideneacetylacetoneethylthiosemicarbazone (CAET)/3‐cinnamalideneacetylacetonephenylthiosemicarbazone (CAPT)] and their copper/zinc complexes were synthesized. They were characterized by analytical and spectral techniques. From these data it was found that the ligands adopt square‐planar geometry on metalation with Cu²⁺ and Zn²⁺. To evaluate the antitumor and cytotoxic activity of the synthesized complexes in mice and human cancer cell lines, the antitumor activity of the complexes was evaluated against an Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time and short‐term in vitro cytotoxic activity. Oral administration of complexes (100 mg/kg) increased the survival time. The cytotoxic activity of complexes was evaluated using human breast cancer (MDA‐MB‐231), colon cancer (HCT‐116) and nonsmall lung cancer (NCI‐H‐23) cell lines. Both the complexes possessed significant antitumor and cytotoxic activity on EAC and human cancer cell lines. The in vitro antimicrobial screening effect of the investigated compounds was also tested against the various organisms by well diffusion method. Copyright © 2009 John Wiley & Sons, Ltd.     

New potential antitumor quinazolinones derived from dynamic 2-undecyl benzoxazinone: Synthesis and cytotoxic evaluation

Since the quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors, a new series of 6-iodo-2-undecylquinazolin-4(3H)-ones were prepared via reaction of 6-iodo-2-undecyl-4H-benzoxazin-4-one with nitrogen nucleophiles, namely, primary amines, 4-amino antipyrine, hydrazine hydrate, diamines, ethanol amine, and/or hydrazide derivatives and screened for their antitumor activity in vitro against a panel of three human tumor cell lines namely; hepatocellular carcinoma (liver) HepG2, colon cancer HCT-116, and mammary gland breast MCF-7. Compounds 14, 16, and 18 showed remarkable broad spectrum antitumor activity. All compounds were fully characterized by means of IR, MS, and ¹H-NMR spectra.     

Nucleic acid-binding comparative studies and cytotoxic properties of a Ru(II) complex

The comparative studies on the interaction of a ruthenium(II) complex [Ru(IP)₂DPBPD(NH₂)₂]²⁺ (1) {IP?=?imidazole[4,5-f] [1,10] phenanthroline, DPBPD(NH₂)₂?=?2,4,5,6-tetraaminopyrimidine-[3,2-a:2??,3??-c]-phenazine} with CT-DNA (calf thymus DNA) and yeast tRNA have been investigated by different spectrophotometric methods and viscosity measurements. The antitumor activities of complex 1 have been evaluated by MTT {MTT?=?(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} method. On the basis of the spectroscopic results, the binding mode of complex 1 to CT-DNA and yeast tRNA are intercalation, and RNA binding of complex 1 is stronger than DNA binding. Furthermore, complex 1 is a better candidate for an enantioselective binder to yeast tRNA than to CT-DNA. The results can be explained by the different structure and configuration between CT-DNA and yeast tRNA reasonably, suggesting that the configuration and structure of nucleic acids have significant effects on the binding behaviors of metal complexes. On the other hand, the complex demonstrates different antitumor activity against selected tumor cell lines in vitro.     

Boronated derivatives of protohemin IX with L-amino acids as potential anticancer agents

New water-soluble conjugates of protohemin IX with an anionic 1-carba-closo-dodecaborate polyhedron and L-amino acids have been synthesized. In these compounds, the amino acid residues are bound to the porphyrin ring through the amide or ester bond. The new water-soluble amino acid derivatives of boronated protohemin IX show high antitumor activity for human tumor cell lines.     

Multispectroscopic DNA interaction studies of a water-soluble nickel(II) complex containing different dinitrogen aromatic ligands

The water-soluble Ni(II) complex, [Ni(bipy)₂(phen-dione)](OAc)₂·2H₂O (bipy = 2,2′-bipyridine and phen-dione = 1,10-phenanthroline-5,6-dione) has been synthesized and characterized by physico-chemical and spectroscopic methods. The binding interactions of this complex with calf thymus DNA (CT-DNA) were investigated using fluorimetry, spectrophotometry, circular dichroism and viscosimetry. In fluorimetric studies, the enthalpy and entropy of the reaction between the complex and CT-DNA showed that the reaction is exothermic (ΔH = −123.9 kJ mol⁻¹; ΔS = −323.5 J mol⁻¹ K⁻¹). The competitive binding studies showed that the complex could not release methylene blue completely. The complex showed absorption hyperchromism in its UV–Vis spectrum with DNA. The calculated binding constant, K _b obtained from UV–Vis absorption studies was 2 × 10⁵ M⁻¹. Moreover, the complex induced detectable changes in the CD spectrum of CT-DNA, as well as changes in its viscosity. The results suggest that this nickel(II) complex interact with CT-DNA via a groove-binding mode.     

Ferrocene‐substituted 3,3′‐diindolylmethanes with improved anticancer activity

A series of ferrocene‐substituted derivatives ( 2a , 2b , 2c , 2d , 2e , 2f , 2g ) of the known drug 3,3′‐diindolylmethane ( DIM ) were prepared and tested for their in vitro antitumor activity. The derivatives 2a (featuring indole moiety), 2b (featuring 2‐methylindole moiety) and 2f (featuring 5‐nitroindole moiety) were growth‐inhibiting in vitro at lower concentrations than DIM in various tumor cells including pancreas cancer (BcPC‐3), three DIM‐resistant cancer cell lines (518 A2, KB‐V1/Vbl, HT‐29), triple‐negative breast cancer (MDA‐MB‐231) and prostate cancer (PC‐3). Derivatives 2a , 2b and 2f were the most active compounds of this series, qualifying as drug candidates for various cancer diseases. Copyright © 2016 John Wiley & Sons, Ltd.     

Nucleic Acid Binding Behavior and Cytotoxicity Properties of a Ruthenium(II) Polypyridyl Complex

The binding of [Ru(IP)₂(dppz-11-CO₂Me)]²⁺ (1) {IP = imidazo[4,5-f][1,10]phenanthroline, dppz-11-CO₂Me = dipyrido[3,2-a:2′,3′-c]phenazine-11-carboxylic acid methyl ester} to calf thymus DNA and yeast tRNA has been investigated by UV–Vis spectroscopy, fluorescence spectroscopy, viscosity, as well as equilibrium dialysis and circular dichroism. In addition, the antitumor activities of complex 1 have been evaluated by the MTT method. On the basis of the spectroscopic results, the binding mode of complex 1 to CT-DNA and yeast tRNA is intercalation. However, DNA binding with complex 1 is stronger than RNA binding with complex 1, and complex 1 is a better candidate for an enantioselective binder to CT-DNA than to yeast tRNA. These results indicate that the structures of DNA and RNA have significant effects on the binding behaviors of complex 1. Furthermore, complex 1 demonstrates different antitumor activities against selected cancer cell lines in vitro.     

Synthesis,structure, protein binding,and cytotoxicity of zinc(II) complexes with tridentate NNO Schiff-base ligands

Mononuclear and trinuclear zinc(II) complexes (1 and 2) with tridentate NNO Schiff-base ligands (HL¹?=?N-2-pyridiylmethylidene-4-chloro-2-hydroxy-phenylamine, HL²?=?N-2-pyridiylmethylidene-2-hydroxy-5-chloro-phenylamine) have been synthesized and characterized by single-crystal X-ray diffraction and elemental analysis. The binding properties of zinc(II) complexes with calf thymus DNA (CT-DNA) and HSA were investigated by UV–visible, fluorescence, and circular dichroism spectra. The zinc(II) complexes bind significantly to CT-DNA by intercalation and bind to protein HSA through a static quenching mechanism. The in vitro cytotoxicity of the complexes on human tumor cells lines was assessed by 3-(4,5-dimathylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, Hoechst 33258 staining experiments.     

Synthesis,DNA-binding,and antitumor activity of polypyridyl-ruthenium(II) complexes [Ru(L)2(DClPIP)] (L = bpy,phen; DClPIP = 2-(2,4-dichlorophenyl)-1H-imidazo[4,5-f][1, 10]phenanthroline)

Abstract

Two new ruthenium(II) complexes, [Ru(bpy)₂(DClPIP)](ClO₄)₂ (1) and [Ru(phen)₂(DClPIP)](ClO₄)₂ (2) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, and DClPIP = 2-(2,4-dichlorophenyl)-1H-imidazo[4,5-f][1, 10]phenanthroline), have been prepared in high yield by using microwave-assisted synthesis technology. The anticancer activity of the two ruthenium(II) complexes against A549, C6, CNE-1 and MDA-MB-231 cell lines has been evaluated by MTT assay and results showed that 2 exhibited higher antitumor activity than 1 toward all the selected tumor cell lines. Besides, A549 cell line was sensitive to both ruthenium(II) complexes, especially to 2 (IC₅₀ = 8.01?±?0.36?μM). Meanwhile, 2 showed low toxicity against MCF-10A human normal cells. Furthermore, the DNA-binding properties of the two new ruthenium(II) complexes with CT-DNA have been investigated by electronic absorption titration, luminescence spectra, circular dichroism spectra and viscosity measurements. The results suggested that 1 and 2 were able to interact with CT-DNA via intercalative mode with a strong binding affinity in the order 2?>?1. All of these results suggested that anticancer activity of both ruthenium(II) complexes could be closely related to their interaction with DNA.