含硅二烃基锡异羟肟酸配合物的合成及结构表征
摘要
自从Brown在1972年首次发现Ph3SnO2CCH3具有抑制小鼠肿瘤的生长作用以来,人们对有机锡(Ⅳ)化合物的抗癌活性方面进行了广泛的研究。一些有机锡化合物的抗癌活性强于临床上使用的顺铂,有研究表明含硅二烃基锡化合物在抗癌方面具有较强的活性,本论文在此研究基础上设计并合成9个新的以异羟肟酸为配体的含硅二烃基锡配合物。
(1)4个二硅烃基锡二异羟肟酸配合物：(Me3SiCH2)2Sn{RC(O)NHO}2 (R=C6H5；p-ClC6H4；CH3CH2CH2；CH3CH2CH2CH2CH2)
(2)4个混合含硅二烃基锡二异羟肟酸配合物：R(Me3 SiCH2)Sn{R'C(O)NHO}2 (R=Ph,R'=CH3CH2CH2；R=Ph,R'=CH3CH2CH2CH2CH2:R=Bu,R'= CH3CH2CH2CH2CH2；R=Cy,R'=CH3CH2CH2CH2CH2)
(3)1个二硅烃基锡单异羟肟酸配合物{(Me3SiCH2)2SnC6H4C(O)NHO}2O
本论文对合成方法进行了优化,通过红外光谱、1H NMR.13C NMR及元素分析对其结构进行了的表征,确定了所有目标化合物的分子结构：是以锡原子为中心的O-O鳌合型配合物,并对水溶性进行了初步实验。
It has been widely researched to the anticancer activities of Organotin (Ⅳ) compounds since Brown first revealed that Ph3SnO2CCH3 could inhibit the growth of tumor in rats. Some organotins exhibit better antiproliferative properties in vitro than cisplatin used for clinical treatment. Numerous studies have shown that diorganotin containing silicon compounds has stronger anticancer activity. Based on the research above, this paper design and synthesize 9 diorganotin hydroxamates containing silicon compounds.
(1) Four new diorganotin dihydroxamates containing silicon: (Me3SiCH2)2Sn{RC(O)NHO}2 (R=C6H5, p-ClC6H4, CH3CH2CH2, CH3CH2CH2CH2CH2)
(2) Four new mixed diorganotin dihydroxamates containing silicon: R(Me3SiCH2)Sn{R'C(O)NHO}2 (R=Ph, Bu, Cy; R'=CH3CH2CH2, CH3CH2CH2CH2CH2)
(3) One new diorganotin monohydroxamates containing silicon: {(Me3SiCH2)2SnC6H4C(O)NH}2O
In this paper, the synthesis method was optimized. The compound structure was characterized with IR,1H NMR,13C NMR spectrometer and elementary analysis, and the result showed that the compounds were O-O chelating compounds. the water-solubility was preliminarily tested.
(1)4个二硅烃基锡二异羟肟酸配合物：(Me3SiCH2)2Sn{RC(O)NHO}2 (R=C6H5；p-ClC6H4；CH3CH2CH2；CH3CH2CH2CH2CH2)
(2)4个混合含硅二烃基锡二异羟肟酸配合物：R(Me3 SiCH2)Sn{R'C(O)NHO}2 (R=Ph,R'=CH3CH2CH2；R=Ph,R'=CH3CH2CH2CH2CH2:R=Bu,R'= CH3CH2CH2CH2CH2；R=Cy,R'=CH3CH2CH2CH2CH2)
(3)1个二硅烃基锡单异羟肟酸配合物{(Me3SiCH2)2SnC6H4C(O)NHO}2O
本论文对合成方法进行了优化,通过红外光谱、1H NMR.13C NMR及元素分析对其结构进行了的表征,确定了所有目标化合物的分子结构：是以锡原子为中心的O-O鳌合型配合物,并对水溶性进行了初步实验。
It has been widely researched to the anticancer activities of Organotin (Ⅳ) compounds since Brown first revealed that Ph3SnO2CCH3 could inhibit the growth of tumor in rats. Some organotins exhibit better antiproliferative properties in vitro than cisplatin used for clinical treatment. Numerous studies have shown that diorganotin containing silicon compounds has stronger anticancer activity. Based on the research above, this paper design and synthesize 9 diorganotin hydroxamates containing silicon compounds.
(1) Four new diorganotin dihydroxamates containing silicon: (Me3SiCH2)2Sn{RC(O)NHO}2 (R=C6H5, p-ClC6H4, CH3CH2CH2, CH3CH2CH2CH2CH2)
(2) Four new mixed diorganotin dihydroxamates containing silicon: R(Me3SiCH2)Sn{R'C(O)NHO}2 (R=Ph, Bu, Cy; R'=CH3CH2CH2, CH3CH2CH2CH2CH2)
(3) One new diorganotin monohydroxamates containing silicon: {(Me3SiCH2)2SnC6H4C(O)NH}2O
In this paper, the synthesis method was optimized. The compound structure was characterized with IR,1H NMR,13C NMR spectrometer and elementary analysis, and the result showed that the compounds were O-O chelating compounds. the water-solubility was preliminarily tested.
引文
[1]Thoonen S H L, Deelman B J and van Koten G. Synthetic aspects of tetraorganotins and organotin(Ⅳ) halides[J]. Journal of Organometallic Chemistry.2004,689(13):2145～2157.
[2]Hadjikakou S K and Hadjiliadis N. Antiproliferative and anti-tumor activity of organotin compounds[J]. Coordination Chemistry Reviews.2009,253 (1-2):235～249.
[3]Pellerito C, Nagy L, Pellerito L, et al. Biological activity studies on organotin (Ⅳ)n+ complexes and parent compounds[J]. Journal of Organometallic Chemistry.2006, 691(8):1733～1747.
[4]Sakho A M, Du D F, Li W J, et al. Synthesis, crystal structures, and antitumor activity of three new organotin carboxylates[J]. Heteroatom Chemistry.2010,21(5):304～313.
[5]Ahmad M S. Biological screening of organotin(Ⅳ) Complexes [D]. Quaid-i-Azam University Islamabad-Pakistan 2008.
[6]Danish M, Ali S, Mazhar M, et al. Mossbauer, multinuclear magnetic resonance and mass spectrometric studies of organotin carboxylates of m-methyltrans-cinnamic acid [J]. Polyhedron.1995,14(20-21):3115～3123.
[7]Miller J M, Luo Y and Wharf I. Studies in aryltin chemistry. Part Ⅱ. The effects of substituent type and position on the disintegration patterns in the mass spectra of Ar4Sn and Ar3SnX compounds[J]. Journal of Organometallic Chemistry.1997,542(1):89～98.
[8]Sandhu G and Hundal R. Preparation, IR,13C and 119mSn Mossbauer spectral studies of organotin(Ⅳ) derivatives of ethylenediaminetetraacetic acid [J]. Journal of Organometallic Chemistry.1992,436(3):287～298.
[9]Muhammad N, Shuja S, Ali S, et al. New dimeric, trimeric and supramolecular organotin (Ⅳ) dithiocarboxylates:Synthesis, structural characterization and biocidal activities[J]. Polyhedron.2009,28(16):3439～3448.
[10]Sawyer A K and Kuivila H G.1,2-Diacyloxyditins:A new class of organotin compound1[J]. The Journal of Organic Chemistry.1962,27(2):610～614.
[11]Wu X, Kang W, Zhu D, et al. Synthesis, crystal structure and biological activities of two novel organotin (Ⅳ) complexes constructed from 12-(4-methylbenzoyl)-9,10-dihydro-9, 10-ethanoanthracene-11-carboxylic acid[J]. Journal of Organometallic Chemistry.2009, 694(18):2981～2986.
[12]Muhammad N, Zia ur R, Ali S, et al. Organotin(Ⅳ) 4-methoxyphenylethanoates:Synthesis, spectroscopic characterization, X-ray structures and in vitro anticancer activity against human prostate cell lines (PC-3)[J]. Inorganica Chimica Acta.2009,362(8):2842～2848.
[13]Muhammad N and Shah A. Organotin (Ⅳ) 4-nitrophenylethanoates:Synthesis, structural characteristics and intercalative mode of interaction with DNA[J]. Journal of Organometallic Chemistry.2009,694(21):3431～3437.
[14]Siddiqi Z A, Shahid M, Kumar S, et al. Synthesis, crystal structure and in vitro antitumor activity of carboxylate bridged dinuclear organotin (Ⅳ) complexes[J]. Journal of Organometallic Chemistry.2009,694(23):3768～3774.
[15]Assunta Costa M, Gulino L, Pellerito L, et al. Effects of two organotin (Ⅳ)(sulfonatophenyl) porphinates on MAPKs and on the growth of A375 human melanoma cells[J]. Oncology Reports.2009,21(3):593～599.
[16]高中军,刘广军,尹汉东.有机锡(Ⅳ)配合物{[(n-C4H9)2 Sn(0.5.O2CCH2C12H8 N)(0.5.C2H50)]20}2.(C12H8NH)的合成、结构和抑瘤活性[J].应用化学.2009,26(2)：140-143.
[17]Gomez-Ruiz S, Kalu erovic G N, Prashar S, et al. Study of the cytotoxic activity of di and triphenyltin (IV) carboxylate complexes[J]. Journal of Inorganic Biochemistry.2008, 102(12):2087～2096.
[18]Tian L, Liu X, Zheng X, et al. Synthesis, characterization, and in vitro cytotoxicity of organotin derivatives of 4-biphenylcarboxylic acid[J]. Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry.2010,40(10):779～784.
[19]Basu Baul T S, Paul A, Pellerito L, et al. Molecular basis of the interaction of novel tributyltin (IV) 2/4-[(E)-2-(aryl)-1-diazenyl] benzoates endowed with an improved cytotoxic profile:Synthesis, structure, biological efficacy and QSAR studies[J]. Journal of Inorganic Biochemistry.2010,104(9):950～966.
[20]Verginadis, Ⅱ, Karkabounas S, Simos Y, et al. Anticancer and cytotoxic effects of a triorganotin compound with 2-mercapto-nicotinic acid in malignant cell lines and tumor bearing Wistar rats[J]. European Journal of Pharmaceutical Sciences.2010,42(3):253～261.
[21]Kang W, Wu X and Huang J. Synthesis, crystal structure and biological activities of four novel tetranuclear di-organotin (Ⅳ) carboxylates[J]. Journal of Organometallic Chemistry. 2009,694(15):2402～2408.
[22]Abdellah M A, Hadjikakou S K, Hadjiliadis N, et al. Synthesis, characterization, and biological studies of organotin (Ⅳ) derivatives withoff-or p-hydroxybenzoic acids[J]. Bioinorganic Chemistry and Applications.2009,13:doi:10.1155/2009/542979.
[23]Li Q S, Guedes da Silva M F C and Pombeiro A J L. Diorganotin(Ⅳ) derivatives of substituted benzohydroxamic acids with high antitumor activity[J]. Chemistry-a European Journal.2004,10(6):1456～1462.
[24]Li Y, Niu X, Jie L, et al. Synthesis and antitumor activity of a new mixed-ligand complex di-n-butyl-(4-chlorobenzohydroxamato) tin (Ⅳ) chloride[J]. Journal of Inorganic Biochemistry.2008,102(9):1731～1735.
[25]Li Q S, Guedes da Silva M F C, Zhao J H, et al. Diorganotin(Ⅳ) derivatives of arylhydroxamic acids:synthesis, properties and antitumor activity [J]. Journal of Organometallic Chemistry.2004,689(24):4584～4591.
[26]尚先梅,吴军,李青山.芳香异羟肟酸有机锡抗癌化合物的初步构效关系[J].中国科学(B辑：化学).2008,38(5)：429-440.
[27]Shang X, Cui J, Wu J, et al. Polynuclear diorganotin (IV) complexes with arylhydroxamates: Syntheses, structures and in vitro cytotoxic activities[J]. Journal of Inorganic Biochemistry. 2008,102(4):901～909.
[28]李云兰,李青山.二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT)的药代动力学和抗癌作用机制研究[D].山西医科大学.2008.
[29]李云兰,牛晓强,李青山.芳香异羟肟酸二丁基锡类抗癌化合物DBDCT和DBDMT在大鼠体内组织分布的比较[J].中国科学：化学.2010,40(11)：1674-1681.
[30]Li Y, Liu J and Li Q. Mechanisms by Which the Antitumor Compound Di-n-Butyl-Di-(4-Chlorobenzohydroxamato)Tin(IV) Induces Apoptosis and the Mitochondrial-Mediated Signaling Pathway in Human Cancer SGC-7901 Cells[J]. Molecular Carcinogenesis.2010,49(6):566-581.
[31]Wiecek J, Kovala-Demertzi D, Ciunik Z, et al. Diorganotin complexes of a thiosemicarbazone, synthesis:properties, X-Ray crystal structure, and antiproliferative activity of diorganotin complexes[J]. Bioinorganic Chemistry and Applications.2010:doi:10. 1155/2010/867195.
[32]Wiecek J, Kovala-Demertzi D, Ciunik Z, et al. Organotin compound derived from 3-hydroxy-2-formylpyridine semicarbazone:synthesis, crystal structure, and antiproliferative Activity[J]. Bioinorganic Chemistry and Applications.2010:doi:10.1155/2010/718606.
[33]Wiecek J, Dokorou V, Ciunik Z, et al. Organotin complexes of pyruvic acid thiosemicarbazone:Synthesis, crystal structures and antiproliferative activity of neutral and cationic diorganotin complexes[J]. Polyhedron.2009,28(15):3298～3304.
[34]Mendes I C, Moreira J P, Ardisson J D, et al. Organotin (Ⅳ) complexes of 2-pyridineformamide-derived thiosemicarbazones:Antimicrobial and cytotoxic effects[J]. European Journal of Medicinal Chemistry.2008,43(7):1454～1461.
[35]Basu Baul T S, Basu S, de Vos D, et al. Amino acetate functionalized Schiff base organotin (IV) complexes as anticancer drugs:synthesis, structural characterization, and in vitro cytotoxicity studies[J]. Investigational New Drugs.2009,27(5):419～431.
[36]Nath M, Yadav R, Eng G, et al. Characteristic spectral studies and in vitro Antimicrobial and in vivo multi-infection antifungal activities in mice of new organotin (IV) derivatives of heterocyclic amino acids[J]. Applied Organometallic Chemistry.1999,13(1):29～37.
[37]Sandhu G and Kaur G. Preparation, IR and 1H NMR spectral studies of triorganotin (IV) complexes of N-benzoylglycine and N-benzoylglycylglycine[J]. Journal of Organometallic Chemistry.1990,388(1-2):63～70.
[38]Nath M, Yadav R, Eng G, et al. Characteristic spectral studies, and antimicrobial and anti-inflammatory activities of diorganotin (Ⅳ) derivatives of dipeptides[J]. Journal of Organometallic Chemistry.1999,577(1):1-8.
[39]Nath M, Pokharia S and Yadav R. Organotin (IV) complexes of amino acids and peptides[J]. Coordination Chemistry Reviews.2001,215(1):99-149.
[40]Gielen M, Biesemans M and Willem R. Organotin compounds:from kinetics to stereochemistry and antitumour activities[J]. Applied Organometallic Chemistry.2005, 19(4):440～450.
[41]Girasolo M A, Rubino S, Portanova P, et al. New organotin(Ⅳ) complexes with L-Arginine, N-alpha-t-Boc-L-Arginine and L-Alanyl-L-Arginine:Synthesis, structural investigations and cytotoxic activity[J]. Journal of Organometallic Chemistry.2010,695(4):609～618.
[42]Basu Baul T S and de Vos D. In vitro cytotoxic evaluation of novel dichlorodiorgano [N-(2-pyridylmethylene) arylamine] tin (Ⅳ) derivatives in human tumor cell lines[J]. Investigational New Drugs.2010,28(5):609～614.
[43]Koch B, Basu Baul T S and Chatterjee A. p53-dependent antiproliferative and antitumor effect of novel alkyl series of diorganotin (Ⅳ) compounds[J]. Investigational New Drugs. 2009,27(4):319～326.
[44]Xanthopoulou M N, Hadjikakou S K, Hadjiliadis N, et al. Biological studies of new organotin (Ⅳ) complexes of thioamide ligands[J]. European Journal of Medicinal Chemistry. 2008,43(2):327～335.
[45]Hadjikakou S, Ozturk I, Xanthopoulou M, et al. Synthesis, structural characterization and biological study of new organotin (Ⅳ), silver (Ⅰ) and antimony (Ⅲ) complexes with thioamides[J]. Journal of Inorganic Biochemistry.2008,102(5-6):1007～1015.
[46]Khan S, Nami S A A and Siddiqi K. Mononuclear indolyldithiocarbamates of SnC14 and R2SnC12:Spectroscopic, thermal characterizations and cytotoxicity assays in vitro[J]. Journal of Organometallic Chemistry.2008,693(6):1049～1057.
[47]Carraher C E, Roner M R, Shahi K, et al. Synthesis and initial cell line results of organotin polyethers containing diethylstilbestrol[J]. Journal of Inorganic and Organometallic Polymers and Materials.2008,18(1):180～188.
[48]Barot G, Roner M R, Naoshima Y, et al. Synthesis, Structural characterization, and preliminary biological characterization of organotin polyethers derived from hydroquinone and substituted hydroquinones[J]. Journal of Inorganic and Organometallic Polymers and Materials.2009,19(1):12～27.
[49]Carraher C E, Battin A, Shahi K R, et al. Synthesis, structural characterization, and initial evaluation as anticancer drugs of dibutyltin polyamines derived from various 4, 6-diaminopyrimidines[J]. Journal of Inorganic and Organometallic Polymers and Materials. 2007,17(4):631-639.
[50]Carraher C E, Sabir T S, Roner M R, et al. Synthesis of organotin polyamine ethers containing acyclovir and their preliminary anticancer and antiviral activity[J]. Journal of Inorganic and Organometallic Polymers and Materials.2006,16(3):249～257.
[51]Barot G, Shahi K R, Roner M R, et al. Synthesis, structural characterization, and ability to inhibit cancer growth of a series of organotin poly(ethylene glycols)[J]. Journal of Inorganic and Organometallic Polymers and Materials.2007,17(4):595～603.
[52]Roner M R, Shahi K R, Barot G, et al. Preliminary results for the inhibition of pancreatic cancer cells by organotin polymers[J]. Journal of Inorganic and Organometallic Polymers and Materials.2009,19(3):410～414.
[53]Etaiw S E H, Sultan A S and El-bendary M M. In vitro and in vivo antitumor activity of novel 3D-organotin supramolecular coordination polymers based on CuCN and pyridine bases[J]. Journal of Organometallic Chemistry.2011,696(8):1668～1676
[54]Kalu erovic G N, Paschke R, Prashar S, et al. Synthesis, characterization and biological studies of 1-D polymeric triphenyltin (Ⅳ) carboxylates[J]. Journal of Organometallic Chemistry.2010,695(15-16):1883～1890.
[55]Dokorou V, Primikiri A and Kovala-Demertzi D. The triphenyltin(Ⅵ) complexes of NSAIDs and derivatives. Synthesis, crystal structure and antiproliferative activity. Potent anticancer agents[J]. Journal of Inorganic Biochemistry.2011,105(2):195～201.
[56]Kovala-Demertzi D, Dokorou V, Primikiri A, et al. Organotin meclofenamic complexes: Synthesis, crystal structures and antiproliferative activity of the first complexes of meclofenamic acid-Novel anti-tuberculosis agents[J]. Journal of Inorganic Biochemistry. 2009,103(5):738-744.
[57]Quidville V, Segond N, Pidoux E, et al. Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer:implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase[J]. Endocrinology.2004,145(5):2561～2571.
[58]Tabassum S, Khan R A, Arjmand F, et al. Synthesis and characterization of glycoconjugate Tin (Ⅳ) complexes:in vitro DNA binding studies, cytotoxicity, and cell death[J]. Journal of Organometallic Chemistry.2011,696(8):1600～1608
[59]Alama A, Viale M, Cilli M, et al. In vitro cytotoxic activity of tri-n-butyltin (Ⅳ) lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo[J]. Investigational New Drugs.2009,27(2):124～130.
[60]Vasilios I. Crystal structure and antitumor activity of the novel zwitterionic complex of tri-n-butyltin (Ⅳ) with 2-thiobarbituric acid[J]. Bioinorganic Chemistry and Applications. 2008,2008:doi:10.1155/2008/654137.
[61]Tabassum S and Pettinari C. Chemical and biotechnological developments in organotin cancer chemotherapy [J]. Journal of Organometallic Chemistry.2006,691(8):1761-1766.
[62]余邦良,马亚平,刘全忠等.铂类抗癌药物研究进展[J].海南大学学报：自然科学版.2005,23(1)：72-80.
[63]Crowe A J, Smith P J, Cardin C J, et al. Possible pre-dissociation of diorganotin dihalide complexes relationship between antitumour activity and structure[J]. Cancer Letters.1984, 24(1):45～48.
[64]李青山,李庭芳,杨慧元等1.4-酰基-5-吡唑酮的二烃基锡配合物的合成、表征及其抗癌活性研究[J].药学学报.2000,35(9)：659-662.
[65]Barbieri R. QSAR approach to understand the antitumour activity of organotins[J]. Inorganica Chimica Acta.1992,191(2):253-259.
[66]Crowe A J, Smith P J and Atassi G. Investigations into the Antitumour activity of organtin compounds.2. diorganotin dihalide and dipseudohalide complexes[J]. Inorganica Chimica Acta-Bioinorganic Chemistry.1984,93(4):179～184.
[67]宁美英,李庭芳,李青山.1,3-二甲基-4-酰基-5-吡唑酮二烃基锡抗癌配合物与单核苷酸作用的研究[J].药学学报.2002,37(6)：433-436.
[68]李青山,频杨,王宏飞等.二氯二苯基锡与单核苷酸配位作用的研究[J].高等学校化学学报.1996,17(8)：1165-1168.
[69]李青山,刘锐铃,黄计军等.二氯二乙基锡与DNA作用的研究[J].高等学校化学学报.2000,21(4)：513-516.
[70]Penninks A H and Seinen W. Mechanisms of dialkyltin induced immunopathology[J]. Veterinary Quarterly.1984,6(4):209～215.
[71]Saxena A and Huber F. Organotin compounds and cancer chemotherapy[J]. Coordination Chemistry Reviews.1989,95(1):109～123.
[72]Prasad K S, Kumar L S, Prasad M, et al. Novel organotin(Ⅳ)-schiff base complexes: synthesis, characterization, Antimicrobial activity, and DNA interaction studies[J]. Bioinorganic Chemistry and Applications.2010:doi:10.1155/2010/854514
[73]杨频,李青山.芳香异羟肟酸二烃基锡配合物的合成、表征及其抗癌活性的研究[J].结构化学.1996,15(02)：163-169.
[74]杨频,郭茂林.金属抗癌剂研究进展与两极互补理论[J].化学通报.1996,(1)：6-11.
[75]尚先梅,吴军and李青山.芳香异羟肟酸有机锡抗癌化合物的初步构效关系[J].中国科学.2008,38(5)：429-440.
[76]Shang X M, Wu J Z and Li Q S. New coordination modes of substituted benzohydroxamic acid with dialkyltin(Ⅳ):Structural diversity through ligand isomerization[J]. European Journal of Inorganic Chemistry.2006, (20):4143～4150.
[77]韩广甸,赵树伟,李述文.有机制备手册第一版(北京化学工业出版社)[M].1980
[78]国家药典编委会.中国华人民共和国药典(2010年版).中国医药出版社[M].2010.
[79]赵敬华,李青山.糠酰异羟肟酸类有机锡配合物的合成及其抗癌活性[J].中国药物化学杂志.2006,16(6)：347-351.
[80]尹汉东,王传华,马春林.有机锡氧羧酸簇合物[PhCH2Sn(O)(O2CCH=CHAr)]6的合成、表征和[PhCH2Sn(O)(O2CCH=CHPh)]6的晶体结构[J].有机化学.2003,23(9)：961-966.
[2]Hadjikakou S K and Hadjiliadis N. Antiproliferative and anti-tumor activity of organotin compounds[J]. Coordination Chemistry Reviews.2009,253 (1-2):235～249.
[3]Pellerito C, Nagy L, Pellerito L, et al. Biological activity studies on organotin (Ⅳ)n+ complexes and parent compounds[J]. Journal of Organometallic Chemistry.2006, 691(8):1733～1747.
[4]Sakho A M, Du D F, Li W J, et al. Synthesis, crystal structures, and antitumor activity of three new organotin carboxylates[J]. Heteroatom Chemistry.2010,21(5):304～313.
[5]Ahmad M S. Biological screening of organotin(Ⅳ) Complexes [D]. Quaid-i-Azam University Islamabad-Pakistan 2008.
[6]Danish M, Ali S, Mazhar M, et al. Mossbauer, multinuclear magnetic resonance and mass spectrometric studies of organotin carboxylates of m-methyltrans-cinnamic acid [J]. Polyhedron.1995,14(20-21):3115～3123.
[7]Miller J M, Luo Y and Wharf I. Studies in aryltin chemistry. Part Ⅱ. The effects of substituent type and position on the disintegration patterns in the mass spectra of Ar4Sn and Ar3SnX compounds[J]. Journal of Organometallic Chemistry.1997,542(1):89～98.
[8]Sandhu G and Hundal R. Preparation, IR,13C and 119mSn Mossbauer spectral studies of organotin(Ⅳ) derivatives of ethylenediaminetetraacetic acid [J]. Journal of Organometallic Chemistry.1992,436(3):287～298.
[9]Muhammad N, Shuja S, Ali S, et al. New dimeric, trimeric and supramolecular organotin (Ⅳ) dithiocarboxylates:Synthesis, structural characterization and biocidal activities[J]. Polyhedron.2009,28(16):3439～3448.
[10]Sawyer A K and Kuivila H G.1,2-Diacyloxyditins:A new class of organotin compound1[J]. The Journal of Organic Chemistry.1962,27(2):610～614.
[11]Wu X, Kang W, Zhu D, et al. Synthesis, crystal structure and biological activities of two novel organotin (Ⅳ) complexes constructed from 12-(4-methylbenzoyl)-9,10-dihydro-9, 10-ethanoanthracene-11-carboxylic acid[J]. Journal of Organometallic Chemistry.2009, 694(18):2981～2986.
[12]Muhammad N, Zia ur R, Ali S, et al. Organotin(Ⅳ) 4-methoxyphenylethanoates:Synthesis, spectroscopic characterization, X-ray structures and in vitro anticancer activity against human prostate cell lines (PC-3)[J]. Inorganica Chimica Acta.2009,362(8):2842～2848.
[13]Muhammad N and Shah A. Organotin (Ⅳ) 4-nitrophenylethanoates:Synthesis, structural characteristics and intercalative mode of interaction with DNA[J]. Journal of Organometallic Chemistry.2009,694(21):3431～3437.
[14]Siddiqi Z A, Shahid M, Kumar S, et al. Synthesis, crystal structure and in vitro antitumor activity of carboxylate bridged dinuclear organotin (Ⅳ) complexes[J]. Journal of Organometallic Chemistry.2009,694(23):3768～3774.
[15]Assunta Costa M, Gulino L, Pellerito L, et al. Effects of two organotin (Ⅳ)(sulfonatophenyl) porphinates on MAPKs and on the growth of A375 human melanoma cells[J]. Oncology Reports.2009,21(3):593～599.
[16]高中军,刘广军,尹汉东.有机锡(Ⅳ)配合物{[(n-C4H9)2 Sn(0.5.O2CCH2C12H8 N)(0.5.C2H50)]20}2.(C12H8NH)的合成、结构和抑瘤活性[J].应用化学.2009,26(2)：140-143.
[17]Gomez-Ruiz S, Kalu erovic G N, Prashar S, et al. Study of the cytotoxic activity of di and triphenyltin (IV) carboxylate complexes[J]. Journal of Inorganic Biochemistry.2008, 102(12):2087～2096.
[18]Tian L, Liu X, Zheng X, et al. Synthesis, characterization, and in vitro cytotoxicity of organotin derivatives of 4-biphenylcarboxylic acid[J]. Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry.2010,40(10):779～784.
[19]Basu Baul T S, Paul A, Pellerito L, et al. Molecular basis of the interaction of novel tributyltin (IV) 2/4-[(E)-2-(aryl)-1-diazenyl] benzoates endowed with an improved cytotoxic profile:Synthesis, structure, biological efficacy and QSAR studies[J]. Journal of Inorganic Biochemistry.2010,104(9):950～966.
[20]Verginadis, Ⅱ, Karkabounas S, Simos Y, et al. Anticancer and cytotoxic effects of a triorganotin compound with 2-mercapto-nicotinic acid in malignant cell lines and tumor bearing Wistar rats[J]. European Journal of Pharmaceutical Sciences.2010,42(3):253～261.
[21]Kang W, Wu X and Huang J. Synthesis, crystal structure and biological activities of four novel tetranuclear di-organotin (Ⅳ) carboxylates[J]. Journal of Organometallic Chemistry. 2009,694(15):2402～2408.
[22]Abdellah M A, Hadjikakou S K, Hadjiliadis N, et al. Synthesis, characterization, and biological studies of organotin (Ⅳ) derivatives withoff-or p-hydroxybenzoic acids[J]. Bioinorganic Chemistry and Applications.2009,13:doi:10.1155/2009/542979.
[23]Li Q S, Guedes da Silva M F C and Pombeiro A J L. Diorganotin(Ⅳ) derivatives of substituted benzohydroxamic acids with high antitumor activity[J]. Chemistry-a European Journal.2004,10(6):1456～1462.
[24]Li Y, Niu X, Jie L, et al. Synthesis and antitumor activity of a new mixed-ligand complex di-n-butyl-(4-chlorobenzohydroxamato) tin (Ⅳ) chloride[J]. Journal of Inorganic Biochemistry.2008,102(9):1731～1735.
[25]Li Q S, Guedes da Silva M F C, Zhao J H, et al. Diorganotin(Ⅳ) derivatives of arylhydroxamic acids:synthesis, properties and antitumor activity [J]. Journal of Organometallic Chemistry.2004,689(24):4584～4591.
[26]尚先梅,吴军,李青山.芳香异羟肟酸有机锡抗癌化合物的初步构效关系[J].中国科学(B辑：化学).2008,38(5)：429-440.
[27]Shang X, Cui J, Wu J, et al. Polynuclear diorganotin (IV) complexes with arylhydroxamates: Syntheses, structures and in vitro cytotoxic activities[J]. Journal of Inorganic Biochemistry. 2008,102(4):901～909.
[28]李云兰,李青山.二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT)的药代动力学和抗癌作用机制研究[D].山西医科大学.2008.
[29]李云兰,牛晓强,李青山.芳香异羟肟酸二丁基锡类抗癌化合物DBDCT和DBDMT在大鼠体内组织分布的比较[J].中国科学：化学.2010,40(11)：1674-1681.
[30]Li Y, Liu J and Li Q. Mechanisms by Which the Antitumor Compound Di-n-Butyl-Di-(4-Chlorobenzohydroxamato)Tin(IV) Induces Apoptosis and the Mitochondrial-Mediated Signaling Pathway in Human Cancer SGC-7901 Cells[J]. Molecular Carcinogenesis.2010,49(6):566-581.
[31]Wiecek J, Kovala-Demertzi D, Ciunik Z, et al. Diorganotin complexes of a thiosemicarbazone, synthesis:properties, X-Ray crystal structure, and antiproliferative activity of diorganotin complexes[J]. Bioinorganic Chemistry and Applications.2010:doi:10. 1155/2010/867195.
[32]Wiecek J, Kovala-Demertzi D, Ciunik Z, et al. Organotin compound derived from 3-hydroxy-2-formylpyridine semicarbazone:synthesis, crystal structure, and antiproliferative Activity[J]. Bioinorganic Chemistry and Applications.2010:doi:10.1155/2010/718606.
[33]Wiecek J, Dokorou V, Ciunik Z, et al. Organotin complexes of pyruvic acid thiosemicarbazone:Synthesis, crystal structures and antiproliferative activity of neutral and cationic diorganotin complexes[J]. Polyhedron.2009,28(15):3298～3304.
[34]Mendes I C, Moreira J P, Ardisson J D, et al. Organotin (Ⅳ) complexes of 2-pyridineformamide-derived thiosemicarbazones:Antimicrobial and cytotoxic effects[J]. European Journal of Medicinal Chemistry.2008,43(7):1454～1461.
[35]Basu Baul T S, Basu S, de Vos D, et al. Amino acetate functionalized Schiff base organotin (IV) complexes as anticancer drugs:synthesis, structural characterization, and in vitro cytotoxicity studies[J]. Investigational New Drugs.2009,27(5):419～431.
[36]Nath M, Yadav R, Eng G, et al. Characteristic spectral studies and in vitro Antimicrobial and in vivo multi-infection antifungal activities in mice of new organotin (IV) derivatives of heterocyclic amino acids[J]. Applied Organometallic Chemistry.1999,13(1):29～37.
[37]Sandhu G and Kaur G. Preparation, IR and 1H NMR spectral studies of triorganotin (IV) complexes of N-benzoylglycine and N-benzoylglycylglycine[J]. Journal of Organometallic Chemistry.1990,388(1-2):63～70.
[38]Nath M, Yadav R, Eng G, et al. Characteristic spectral studies, and antimicrobial and anti-inflammatory activities of diorganotin (Ⅳ) derivatives of dipeptides[J]. Journal of Organometallic Chemistry.1999,577(1):1-8.
[39]Nath M, Pokharia S and Yadav R. Organotin (IV) complexes of amino acids and peptides[J]. Coordination Chemistry Reviews.2001,215(1):99-149.
[40]Gielen M, Biesemans M and Willem R. Organotin compounds:from kinetics to stereochemistry and antitumour activities[J]. Applied Organometallic Chemistry.2005, 19(4):440～450.
[41]Girasolo M A, Rubino S, Portanova P, et al. New organotin(Ⅳ) complexes with L-Arginine, N-alpha-t-Boc-L-Arginine and L-Alanyl-L-Arginine:Synthesis, structural investigations and cytotoxic activity[J]. Journal of Organometallic Chemistry.2010,695(4):609～618.
[42]Basu Baul T S and de Vos D. In vitro cytotoxic evaluation of novel dichlorodiorgano [N-(2-pyridylmethylene) arylamine] tin (Ⅳ) derivatives in human tumor cell lines[J]. Investigational New Drugs.2010,28(5):609～614.
[43]Koch B, Basu Baul T S and Chatterjee A. p53-dependent antiproliferative and antitumor effect of novel alkyl series of diorganotin (Ⅳ) compounds[J]. Investigational New Drugs. 2009,27(4):319～326.
[44]Xanthopoulou M N, Hadjikakou S K, Hadjiliadis N, et al. Biological studies of new organotin (Ⅳ) complexes of thioamide ligands[J]. European Journal of Medicinal Chemistry. 2008,43(2):327～335.
[45]Hadjikakou S, Ozturk I, Xanthopoulou M, et al. Synthesis, structural characterization and biological study of new organotin (Ⅳ), silver (Ⅰ) and antimony (Ⅲ) complexes with thioamides[J]. Journal of Inorganic Biochemistry.2008,102(5-6):1007～1015.
[46]Khan S, Nami S A A and Siddiqi K. Mononuclear indolyldithiocarbamates of SnC14 and R2SnC12:Spectroscopic, thermal characterizations and cytotoxicity assays in vitro[J]. Journal of Organometallic Chemistry.2008,693(6):1049～1057.
[47]Carraher C E, Roner M R, Shahi K, et al. Synthesis and initial cell line results of organotin polyethers containing diethylstilbestrol[J]. Journal of Inorganic and Organometallic Polymers and Materials.2008,18(1):180～188.
[48]Barot G, Roner M R, Naoshima Y, et al. Synthesis, Structural characterization, and preliminary biological characterization of organotin polyethers derived from hydroquinone and substituted hydroquinones[J]. Journal of Inorganic and Organometallic Polymers and Materials.2009,19(1):12～27.
[49]Carraher C E, Battin A, Shahi K R, et al. Synthesis, structural characterization, and initial evaluation as anticancer drugs of dibutyltin polyamines derived from various 4, 6-diaminopyrimidines[J]. Journal of Inorganic and Organometallic Polymers and Materials. 2007,17(4):631-639.
[50]Carraher C E, Sabir T S, Roner M R, et al. Synthesis of organotin polyamine ethers containing acyclovir and their preliminary anticancer and antiviral activity[J]. Journal of Inorganic and Organometallic Polymers and Materials.2006,16(3):249～257.
[51]Barot G, Shahi K R, Roner M R, et al. Synthesis, structural characterization, and ability to inhibit cancer growth of a series of organotin poly(ethylene glycols)[J]. Journal of Inorganic and Organometallic Polymers and Materials.2007,17(4):595～603.
[52]Roner M R, Shahi K R, Barot G, et al. Preliminary results for the inhibition of pancreatic cancer cells by organotin polymers[J]. Journal of Inorganic and Organometallic Polymers and Materials.2009,19(3):410～414.
[53]Etaiw S E H, Sultan A S and El-bendary M M. In vitro and in vivo antitumor activity of novel 3D-organotin supramolecular coordination polymers based on CuCN and pyridine bases[J]. Journal of Organometallic Chemistry.2011,696(8):1668～1676
[54]Kalu erovic G N, Paschke R, Prashar S, et al. Synthesis, characterization and biological studies of 1-D polymeric triphenyltin (Ⅳ) carboxylates[J]. Journal of Organometallic Chemistry.2010,695(15-16):1883～1890.
[55]Dokorou V, Primikiri A and Kovala-Demertzi D. The triphenyltin(Ⅵ) complexes of NSAIDs and derivatives. Synthesis, crystal structure and antiproliferative activity. Potent anticancer agents[J]. Journal of Inorganic Biochemistry.2011,105(2):195～201.
[56]Kovala-Demertzi D, Dokorou V, Primikiri A, et al. Organotin meclofenamic complexes: Synthesis, crystal structures and antiproliferative activity of the first complexes of meclofenamic acid-Novel anti-tuberculosis agents[J]. Journal of Inorganic Biochemistry. 2009,103(5):738-744.
[57]Quidville V, Segond N, Pidoux E, et al. Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer:implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase[J]. Endocrinology.2004,145(5):2561～2571.
[58]Tabassum S, Khan R A, Arjmand F, et al. Synthesis and characterization of glycoconjugate Tin (Ⅳ) complexes:in vitro DNA binding studies, cytotoxicity, and cell death[J]. Journal of Organometallic Chemistry.2011,696(8):1600～1608
[59]Alama A, Viale M, Cilli M, et al. In vitro cytotoxic activity of tri-n-butyltin (Ⅳ) lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo[J]. Investigational New Drugs.2009,27(2):124～130.
[60]Vasilios I. Crystal structure and antitumor activity of the novel zwitterionic complex of tri-n-butyltin (Ⅳ) with 2-thiobarbituric acid[J]. Bioinorganic Chemistry and Applications. 2008,2008:doi:10.1155/2008/654137.
[61]Tabassum S and Pettinari C. Chemical and biotechnological developments in organotin cancer chemotherapy [J]. Journal of Organometallic Chemistry.2006,691(8):1761-1766.
[62]余邦良,马亚平,刘全忠等.铂类抗癌药物研究进展[J].海南大学学报：自然科学版.2005,23(1)：72-80.
[63]Crowe A J, Smith P J, Cardin C J, et al. Possible pre-dissociation of diorganotin dihalide complexes relationship between antitumour activity and structure[J]. Cancer Letters.1984, 24(1):45～48.
[64]李青山,李庭芳,杨慧元等1.4-酰基-5-吡唑酮的二烃基锡配合物的合成、表征及其抗癌活性研究[J].药学学报.2000,35(9)：659-662.
[65]Barbieri R. QSAR approach to understand the antitumour activity of organotins[J]. Inorganica Chimica Acta.1992,191(2):253-259.
[66]Crowe A J, Smith P J and Atassi G. Investigations into the Antitumour activity of organtin compounds.2. diorganotin dihalide and dipseudohalide complexes[J]. Inorganica Chimica Acta-Bioinorganic Chemistry.1984,93(4):179～184.
[67]宁美英,李庭芳,李青山.1,3-二甲基-4-酰基-5-吡唑酮二烃基锡抗癌配合物与单核苷酸作用的研究[J].药学学报.2002,37(6)：433-436.
[68]李青山,频杨,王宏飞等.二氯二苯基锡与单核苷酸配位作用的研究[J].高等学校化学学报.1996,17(8)：1165-1168.
[69]李青山,刘锐铃,黄计军等.二氯二乙基锡与DNA作用的研究[J].高等学校化学学报.2000,21(4)：513-516.
[70]Penninks A H and Seinen W. Mechanisms of dialkyltin induced immunopathology[J]. Veterinary Quarterly.1984,6(4):209～215.
[71]Saxena A and Huber F. Organotin compounds and cancer chemotherapy[J]. Coordination Chemistry Reviews.1989,95(1):109～123.
[72]Prasad K S, Kumar L S, Prasad M, et al. Novel organotin(Ⅳ)-schiff base complexes: synthesis, characterization, Antimicrobial activity, and DNA interaction studies[J]. Bioinorganic Chemistry and Applications.2010:doi:10.1155/2010/854514
[73]杨频,李青山.芳香异羟肟酸二烃基锡配合物的合成、表征及其抗癌活性的研究[J].结构化学.1996,15(02)：163-169.
[74]杨频,郭茂林.金属抗癌剂研究进展与两极互补理论[J].化学通报.1996,(1)：6-11.
[75]尚先梅,吴军and李青山.芳香异羟肟酸有机锡抗癌化合物的初步构效关系[J].中国科学.2008,38(5)：429-440.
[76]Shang X M, Wu J Z and Li Q S. New coordination modes of substituted benzohydroxamic acid with dialkyltin(Ⅳ):Structural diversity through ligand isomerization[J]. European Journal of Inorganic Chemistry.2006, (20):4143～4150.
[77]韩广甸,赵树伟,李述文.有机制备手册第一版(北京化学工业出版社)[M].1980
[78]国家药典编委会.中国华人民共和国药典(2010年版).中国医药出版社[M].2010.
[79]赵敬华,李青山.糠酰异羟肟酸类有机锡配合物的合成及其抗癌活性[J].中国药物化学杂志.2006,16(6)：347-351.
[80]尹汉东,王传华,马春林.有机锡氧羧酸簇合物[PhCH2Sn(O)(O2CCH=CHAr)]6的合成、表征和[PhCH2Sn(O)(O2CCH=CHPh)]6的晶体结构[J].有机化学.2003,23(9)：961-966.