2,2’-联吡啶和三氟甲基修饰β-二酮金属钯(Ⅱ)配合物的合成、表征和体外细胞毒性
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摘要
以取代苯乙酮、三氟乙酸乙酯及2,2’-联吡啶硝酸钯为原料,经Claisen缩合反应和螯合反应得到了系列三氟甲基修饰的β-二酮金属钯(Ⅱ)配合物.配合物结构通过了NMR、ESI-MS、IR及元素分析的表征,用X线单晶衍射测定了配合物3g的晶体结构.用MTT法对产物的体外细胞毒性进行了评价.初步结果表明:所得配合物对MCF-7细胞的毒性明显高于Hela和A549细胞,其中配合物3a对MCF-7的细胞毒性与顺铂相当.
A novel series of palladium(Ⅱ)complexes withβ-diketonate ligands functionalized with trifluoromethyl group and 2,2'-bipyridine(bipy)have been synthesized through a directed self-assembly approach that involves spontaneous deprotonation of theβ-diketone ligands in H_2O/acetone solution.These complexes have been characterized by elemental analysis,IR,~1H NMR,and HRMS.Crystal structure of 3g has been determined by X-ray diffraction analysis.The cytotoxicity was tested by MTT assay.The preliminary results showed that most of the obtained complexes were more toxic against MCF-7and Hela than A549 cells.The cytotoxicity of complexes 3ais almost equal to that of cisplatin against MCF-7.
A novel series of palladium(Ⅱ)complexes withβ-diketonate ligands functionalized with trifluoromethyl group and 2,2'-bipyridine(bipy)have been synthesized through a directed self-assembly approach that involves spontaneous deprotonation of theβ-diketone ligands in H_2O/acetone solution.These complexes have been characterized by elemental analysis,IR,~1H NMR,and HRMS.Crystal structure of 3g has been determined by X-ray diffraction analysis.The cytotoxicity was tested by MTT assay.The preliminary results showed that most of the obtained complexes were more toxic against MCF-7and Hela than A549 cells.The cytotoxicity of complexes 3ais almost equal to that of cisplatin against MCF-7.
引文
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[5]WONG E,GIANDOMENICO C M.Current status of platinum-based antitumor drugs[J].Chem Rev,1999,99(9):2451-2466.DOI:10.1021/cr980420v.
[6]GAO E J,LIU C,ZHU M C,et al.Current development of Pd(Ⅱ)complexes as potential antitumor agents[J].Anti-Cancer AgentS in Medicinal Chemistry,2009,9(3):356-368.DOI:10.2174/1871520610909030356.
[7]RAU T,ALSFASSER R,ZAHL A,et al.Structural and kinetic studies on the formation of platinum(Ⅱ)and palladium(Ⅱ)complexes with l-cysteine-derived ligands[J].Inorg Chem,1998,37(17):4223-4230.DOI:10.1021/ic9711574.
[8]KAPDI A R,FAIRLAMB I J S.Anti-cancer palladium complexes:a focus on PdX2L2,palladacycles and related complexes[J].Chem Soc Rev,2014,43:4751-4777.DOI:10.1039/c4cs00063c.
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[10]SHEIKH J,PARVEZ A,JUNEJA H,et al.Synthesis,biopharmaceutical characterization,antimicrobial and antioxidant activities of 1-(4′-O-β-D-glucopyranosyloxy-2′-hydroxyphenyl)-3-aryl-propane-1,3-diones[J].Eur J Med Chem,2011,46(4):1390-1399.DOI:10.1016/j.ejmech.2011.01.068
[11]WILSON J J,LIPPARD S J.In Vitro anticancer activity of cis-diammineplatinum(Ⅱ)complexes withβ-diketonate leaving group ligands[J].J Med Chem,2012,55(11):5326-5336.DOI:10.1021/jm3002857.
[12]ALMEIDA J D C,PAIXAO D A,MARZANO I M,et al.Copper(Ⅱ)complexes withβ-diketones and N-donor heterocyclic ligands:Crystal structure,spectral properties,and cytotoxic activity[J].Polyhedron,2015,89(29):1-8.DOI:10.1016/j.poly.2014.12.026.
[13]LOPESA P S,PAIXAO D A,PAULAB F C S,et al.A new copper(Ⅱ)complex with 2-thenoyltrifluoroacetone and 2,2-bipyridine:Crystal structure,spectral properties and cytotoxic activity[J].J Mol Struct,2013,1034(27):84-88.DOI:10.1016/j.molstruc.2012.09.022.
[14]HUSSAIN A,GADADHAR S,GOSWAMI T K.Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(Ⅲ)complexes of a polypyridyl ligand[J].Dalton Trans,2012,41:885-895.DOI:10.1039/c1dt11400j.
[15]ZHANG K Z,CUI S S,WANG J J,et al.Study on antitumor activity of metal-based diketone complexes[J].Med Chem Res,2012,21(7):1071-1076.DOI:10.1007/s00044-011-9618-0.
[16]VOCK C A,RENFREW A K,SCOPELLITI R,et al.Influence of the diketonato ligand on the cytotoxicities of[Ru(η6-pcymene)(R2acac)(PTA)]+complexes(PTA=1,3,5-triaza-7-phosphaadamantane)[J].Eur J Inorg Chem,2008(10):1661-1671.DOI:10.1002/ejic.200701291.
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[18]WIMMER S,CASTAN P,WIMMER F L,et al.Preparation and interconversion of dimeric di-μ-hydroxo and tri-μ-hydroxo complexes of platinum(Ⅱ)and palladium(Ⅱ)with 2,2′-bipyridine and 1,10-phenanthroline[J].J Chem Soc Dalton Trans,1989,3:403-412.DOI:10.1039/dt9890000403.
[19]GAO Mingzhang,WANG Min,MILLER K D,et al.Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2expression in cancer[J].Eur J Med Chem,2011,46(9):4760-4767.DOI:10.1016/j.ejmech.2011.05.024.
[20]MOSMSNN T.Rapid colorimetric assay for cellular growth and survival:Application to proliferation and cytotoxicity assays[J].J Immunol Methods,1983,65(1-2):55-63.DOI:10.1016/0022-1759(83)90303-4.