同时含α-[Mo8O26]4-和β-[Mo8O26]4-的新型超分子化合物的合成、表征及其抗肿瘤活性

以(NH4)2[Mo4O13]·2H2O, NiCl2·6H2O和2-(1H-吡唑-3-基)吡啶为原料, 通过水热方法合成了一个新颖的[Ni(C8N3H7)3]4[Mo8O26]2·7H2O超分子化合物. 采用元素分析、红外光谱和单晶X射线衍射法表征了该无机-有机杂化配合物的结构. 晶体解析表明, 该化合物同时含有α-[Mo8O26]4-和β-[Mo8O26]4-, 在[Ni(C8N3H7)3]2+阳离子和[Mo8O26]4-阴离子之间通过氢键作用结合, 在[Ni(C8N3H7)3]2+阳离子之间通过芳香环的π-π堆积作用连接, 两种[Mo8O26]4-阴离子作为客体共存于一个具有三维蜂窝状的超分子结构中. 同时研究了该化合物对人卵巢癌细胞SK-OV-3、肺癌细胞A549、宫颈癌细胞Hela和乳腺癌细胞MCF-7等细胞的体外抗肿瘤活性. 结果表明, 该化合物对3种不同来源的肿瘤细胞均有一定的增殖抑制作用, 其中对MCF-7细胞的IC50值为6.48 μmol/L, 具有进一步研究的价值.     

两个取代苄基锡配合物的合成、抗癌活性及其与DNA相互作用

利用二(2,4-二氯苄基)二氯化锡分别与对甲基苯甲酰肼或对叔丁基苯甲酰肼、丙酮酸钠在甲醇中发生反应,合成了2个二(2,4-二氯苄基)锡配合物(C1、C2),通过元素分析、IR、¹H NMR、¹³C NMR、¹¹⁹Sn NMR、HRMS以及X射线单晶衍射表征了配合物结构。测试了配合物C1、C2的热稳定性以及配合物对NCI-H460(人肺癌细胞)、HepG2(人肝癌细胞)和MCF7(人乳腺癌细胞)的体外抑制活性,发现配合物C1对癌细胞均表现较好的抑制作用。利用UV-Vis光谱、荧光光谱以及黏度法研究了2个配合物与ct-DNA之间的相互作用,结果表明配合物是以经典的嵌入模式与DNA结合。     

大黄酸-缬氨酸加合物的合成及初步抗肿瘤活性

以大黄酸为原料,经酯化、烷基化、水解及缩合等反应步骤合成了12个大黄酸-缬氨酸加合物.目标化合物经1H NMR,~(13)C NMR和HRMS进行了结构确证.以顺铂和阿霉素为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物的体外抗肿瘤(Hela,MCF-7,HepG2,KB和HEK293T等5株细胞)活性.结果表明,化合物5l显示出较好的抗肿瘤活性,其IC50值在1.6~9.4μmol/L之间.作用机制研究结果表明,化合物5l能够与DNA发生较强的结合作用.     

2-羰基-3-苯基丙酸芳甲酰腙二(2,4-二氯苄基)锡配合物的合成、晶体结构及生物活性

二(2,4-二氯苄基)二氯化锡分别与2-羰基-3-苯基丙酸苯甲酰腙及2-羰基-3-苯基丙酸水杨酰腙反应,合成了2个取代苄基锡配合物(C1、C2),通过元素分析、IR、1H NMR、13C NMR、119Sn NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞Hela、MCF7、Hep G2、Colo205、NCI-H460以及正常人体胚肾细胞HEK293、正常人体肝细胞HL7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB做为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明:配合物C1、C2对5种癌细胞都有明显的抑制作用,配合物C2对HEK293、HL7702的细胞毒性远小于C1;配合物C1与小牛胸腺DNA作用是插入结合与静电结合共同作用所致,配合物C2与小牛胸腺DNA作用是插入结合作用所致。     

伊马替尼衍生物的合成及其抗肿瘤活性

以4-硝基-2-氨基甲苯为起始原料,经加成、缩合、环化和还原反应制得中间体N-(2-甲基-5-氨基苯基)-4-(3-吡啶基)嘧啶-2-胺(4),再与取代酰氯反应,合成了7个新型伊马替尼衍生物（5a~5g）,其结构经¹H NMR, ¹³C NMR和HR-MS 表征。采用四甲基偶氮唑盐(MTT)法考察了5对人肝癌细胞(HepG₂)、子宫颈癌细胞（Hela）、肺癌细胞（H460）和乳腺癌细胞（MCF-7）体外抑制活性。结果显示：5e体外抑制活性最优,其IC₅₀分别为10.90±1.00 μmol·L^-1; 8.51±0.90 μmol·L^-1; 13.15±1.11 μmol·L^-1; 14.75±0.78 μmol·L^-1。     

Synthesis and antiproliferative activities of thioxoflavonoids on three human cancer cells

Two series of fifteen novel thioxoflavonoids 2a-2h and 4a-4g were synthesized from corresponding flavonoids 1a-1h and 3a-3g by reacting with Lawesson’s reagent, respectively. Their in vitro antiproliferative activities were evaluated on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) using cell counting kit-8 (CCK-8) assay. The results showed that most of the target compounds exhibited moderate to good antiproliferative activities against the three human cancer cell lines. In particular, thioxoflavonoids 2f and 2g showed the strongest antiproliferative activity on all three human cancer cell lines with IC₅₀ values ranging from 3.34 to 4.67 μM, 4f showed the best antiproliferative activity on Hela cells (IC₅₀ 2.30 μM), 2e showed the best antiproliferative activity on HCC1954 cells (IC₅₀ 2.13 μM) and SK-OV-3 cells (IC₅₀ 2.33 μM). The antiproliferative activities may be involved in their antioxidant activity, which can be speculated by their ability to scavenge free radicals and by their capacity of affecting key redox enzymes.     

2-羰基-3-苯基丙酸芳甲酰腙二(2,4-二氯苄基)锡配合物的合成、晶体结构及生物活性

二（2,4-二氯苄基）二氯化锡分别与2-羰基-3-苯基丙酸苯甲酰腙及2-羰基-3-苯基丙酸水杨酰腙反应,合成了2个取代苄基锡配合物（C1、C2）,通过元素分析、IR、¹H NMR、¹³C NMR、¹¹⁹Sn NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞Hela、MCF7、HepG2、Colo205、NCI-H460以及正常人体胚肾细胞HEK293、正常人体肝细胞HL7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB做为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明：配合物C1、C2对5种癌细胞都有明显的抑制作用,配合物C2对HEK293、HL7702的细胞毒性远小于C1;配合物C1与小牛胸腺DNA作用是插入结合与静电结合共同作用所致,配合物C2与小牛胸腺DNA作用是插入结合作用所致。     

Lignan glucoside from Sinopodophyllum emodi and its cytotoxic activity

A new lignan glycoside was isolated from the n-butanol extract of the roots and rhizomes of Sinopodophyllum emodi.On the basis of spectral evidences,its structure was established and named as 4,5-didemethylpodophyllotoxin 7’-O-β-D-glucopyranoside. This compound showed cytotoxicity against four human cancer cell lines(Hela,K562,SH-SY5Y and CNE) in vitro.     

对氯苄基锡酰腙配合物的合成、抗肿瘤活性及其与DNA相互作用

用二对氯苄基二氯化锡分别与对甲基苯甲酰肼缩苯甲酰甲酸及苯甲酰肼缩苯甲酰甲酸反应,合成了2个对氯苄基锡配合物(C1、C2),通过元素分析、IR、1 H NMR、13C NMR、119Sn NMR、HRMS以及X射线单晶衍射等表征了配合物结构。测试了配合物C1、C2的热稳定性以及配合物对癌细胞NCI?H460、HepG2、MCF7的体外抑制活性,发现配合物C2对癌细胞NCI?H460、HepG2、MCF7等均表现出良好的抑制作用。利用紫外吸收光谱、荧光猝灭光谱以及粘度法研究了配合物C2与ct?DNA之间的相互作用,结果表明配合物C2以插入模式与DNA结合。     

基于酰腙配体的双锡核二(2,4-二氯苄基)锡配合物的合成、结构及生物活性

二(2,4-二氯苄基)二氯化锡分别与对甲氧基苯甲酰肼缩2-丁酮酸或2-噻吩酰肼缩2-丁酮酸酸反应,合成了两个二(2,4-二氯苄基)锡配合物(C1、C2),通过傅里叶变换红外光谱仪(FTIR)、核磁共振波谱仪(NMR)、高分辨质谱仪(HRMS)以及X射线单晶衍射(SCXRD)等表征了配合物结构。 两个配合物分子均为双锡核分子,以Sn₂O₂四元环为中心对称,且锡原子与配位原子形成七配位畸变五角双锥构型。 配合物C1、C2在空气氛围,120 ℃以下可稳定存在。 配合物C1、C2对人肺癌细胞(NCI-H460)、人肝癌细胞(HepG2)和人乳腺癌细胞(MCF7)均有较好的抑制作用,配合物C1略优于C2。 配合物C1、C2通过插入结合方式与小牛胸腺DNA相互作用,并且配合物C1与DNA的作用略强于C2。     

Bisarylmaleimides & the Corresponding Indolocarbazoles as Kinase Inhibitors

Cyclin dependent kinases (CDKs) have recently raised considerable attention because of their central role in the regulation of cell cycle progression. A high incidence of genetic mutation of CDK substrates and deregulation of CDK modulators were found in a number of disease states, particularly in cancer. A novel series of unsymmetrical substituted indolocarbazoles were synthesized and their kinase inhibitory capability was evaluated in vitro. 6-Substituted indolocarbazoles were found to b…     

Synthesis and anti-tumour activities of sulphated polysaccharide obtained from Momordica charantia

A native polysaccharide (MCP2) was extracted and isolated from Momordica charantia. Four sulphated derivatives of MCP2 were prepared by chlorosulphonic acid method. The structures of the sulphated derivatives were characterised by FT-IR spectra. Depending on the reaction conditions, the sulphated derivatives showed different degree of substitution (DS) ranging from 0.56 to 1.10, and different weight-average molecular mass (Mw) ranging from 7.2 to 9.3?KDa. It implied the efficient substitution of hydroxyl groups in the polysaccharides by sulphated groups with degradation. The effects of the sulphated derivatives on inhibiting the growth of HepG2 cells and Hela cells in?vitro were compared with taking non-modified MCP2 as control. The sulphated derivatives inhibited the growth of HepG2 cells and Hela cells in?vitro significantly, which indicated that sulphated modification could enhance the anti-tumour activity of MCP2.     

Synthesis, characterization and cytotoxicity of new rotundic acid derivatives

Rotundic acid (RA, 1), a natural compound, exhibits potent tumor cell growth inhibiting properties. To date there are no reports on derivatives of RA. Furthermore, the 28-COOH position of RA might make it unstable and induced serious gastrointestinal side effects when it was applied in vivo. Therefore, in order to explore and make use of this compound, eight new amino acid derivatives of RA at the 28-COOH position were synthesized and evaluated for their cytotoxicities in vitro on three tumor cell lines including A375, HepG2 and NCI-H446. As a result, a few of these new amino acid derivatives showed stronger cytotoxicity. Compound 5a was found to have the best inhibition activity on the three tested human tumor cell lines with IC(50) values of less than 10 μM compared with RA treatment. Meanwhile, the cytotoxicity of compound 6b was significantly higher than that of RA on the A375 cell line and almost the same as RA on the HepG2 and NCI-H446 cell lines. Hence, compounds 5a and 6b may serve as potential lead compounds for the development of new anti-tumor drugs.     

Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells

Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG(2) (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH(2) group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI(50) values (1.30-1.63 μM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels.     

Novel bis(thiosemicarbazones) of the 3,5-diacetyl-1,2,4-triazol series and their platinum(II) complexes: chemistry, antiproliferative activity and preliminary nephrotoxicity studies

The preparation and characterization of three novel (4)N-monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl-1,2,4-triazol series and their dinuclear platinum complexes are described. The crystal and molecular structure of the [Pt(μ-H(3)L(3))](2) complex derived of 3,5-diacetyl-1,2,4-triazol bis((4)N-p-tolylthiosemicarbazone), H(5)L(3), has been resolved by single crystal X-ray diffraction. The ligands coordinate, in an asymmetric dideprotonate form, to the platinum ions in a tridentate fashion (NNS) and S-bridging bonding modes. Thus the molecular units of the platinum complexes are stacked as dimers. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumour properties since are capable of not only circumventing cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in human non-small cell lung cancer NCI-H460 cells. The interactions of these compounds with calf thymus DNA was investigated by UV-vis absorption and a nephrotoxic study, in LLC-PK1 cells, has also been carried out.     

新型含有金刚烷苯乙烯结构单元化合物的合成和初步抗肿瘤增殖

以金刚烷苯乙烯为结构单元,设计合成了3个含有亲水性基团的新型小分子(8a、8b和8c),利用核磁共振谱、红外光谱和高分辨质谱等技术手段对其进行了结构表征。用1-溴代金刚烷作为原料在Pd/C和K2CO3的作用下发生傅克烷基化反应高产率得到金刚烷甲苯(2),随后在N-溴代琥珀酰亚胺(NBS)和(三苯基膦烯基)乙酸甲酯过氧化苯甲酰(BPO)的作用下发生溴代反应得到了金刚烷苄基溴的化合物3,苄基溴在酸性条件下氧化生成醛(4),该醛与维蒂希试剂发生Wittig反应得到甲酸甲酯(5),随后发生碱性条件水解得到重要的中间体6。最后该中间体与3个结构不同的苯胺类化合物发生偶联反应生成了3个目标化合物。通过MTS法评价了3个化合物对人肝癌细胞(SMMC7721)、乳腺癌细胞(MCF-7)、宫颈癌细胞(Hela)、肺癌细胞(A549)的增殖抑制活性。结果表明,部分化合物表现出较好的抑制活性。其中,目标化合物8c对人肝癌细胞表现出较好的抗肿瘤活性(IC_(50)=1.6μmol/L或0.73 mg/L),与现有药物阿霉素相当(0.44 mg/L),有望成为潜在的抗肿瘤药物分子。该类化合物可能在靶向抗肿瘤药物研发方面具有较好的研究前景,所合成的金刚烷苯乙烯类衍生物的抗肿瘤活性、靶点及作用机制还有待进一步研究。     

Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3–11 was synthesised from 5-hydroxy-3,7,3′,4′-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC₅₀ values of 9.51–53.33 μM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4–9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.     

三环己基锡8-羟基喹啉配合物的微波辅助合成、结构表征、热稳定性和体外抗癌活性

微波辐射下,8-羟基喹啉与三环己基氢氧化锡反应,合成了三环己基锡配合物Cy3SnOC9NH6(Cy为环己基)。 通过UV、IR、1H和13C NMR、元素分析及X射线单晶衍射等技术手段表征结构。 实验结果表明,该配合物属三斜晶系,空间群P1,晶体学参数:a=0.99530(5) nm,b=1.01129(5) nm,c=2.58327(13) nm,α=89.1880(10)°,β=86.6290(10)°,γ=81.2490(10)°,Z=4,V=2.5654(2) nm3,Dc=1.326 Mg/m3,μ(MoKα)=1.013 mm-1,F(000)=1064,R1=0.0447,wR2=0.0891。 配合物在200 ℃以下稳定,对人体的癌细胞Colo205、HepG2、MCF-7和NCI-H460增殖均有较强的抑制作用。     

氢键构筑网络结构的三正丁基锡羧酸酯的合成、结构及抗癌活性

微波辐射条件下,μ-氧-双(三正丁基锡)分别与二苯乙醇酸、2-氯烟酸反应,合成了三正丁基锡羧酸酯(n-Bu)₃SnO₂CR(H₂O)[R:C(OH)Ph₂(1),C₅NH₃Cl(2)]。经IR、¹H和¹³C NMR、元素分析及X-射线单晶衍射表征结构。配合物1、2均属正交晶系,空间群分别为Pbca和P2₁2₁2₁,配基与中心锡原子均构成五配位畸变三角双锥构型。1和2晶体中,存在着多种氢键作用,分别连接扩展成二维和三维超分子网络。初步测试表明:1和2对人癌细胞Colo205、HepG2、MCF-7、Hela、NCI-H460增殖均有较强的抑制作用,尤其对MCF-7、Hela、NCI-H460的抑制作用均大大优于卡铂,且1的抗肿瘤活性更优于2。     

Sartoryglabrins, analogs of ardeemins, from Neosartorya glabra

Chemical investigation of a collection of the fungus Neosartorya glabra from Thailand furnished sartoryglabins A-C (1a, 1b and 2) which are analogs of the reverse prenylated indole alkaloids known as (-) ardeemins. Structures of these compounds were established by NMR spectrometry and an X-ray analysis. Sartoryglabins A-C were evaluated for their in vitro growth inhibitory activity on three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma). All the compounds exhibited strong to moderate activity against the MCF-7 cell line but weak or no activity against the NCI-H460 and A375-C5 cell lines. Sartoryglabin B was found to exhibit selectivity towards the MCF-7 cell line.