丁基(乙基二甲基硅基亚甲基)锡二芳香酸酯的合成与结构表征

用丁基(乙基二甲基硅基亚甲基)氧化锡与芳香酸以1∶2的物质的量之比进行反应,合成了5个新的含硅混合二烃基锡化合物——丁基(乙基二甲基硅基亚甲基)锡二芳香酸酯。通过IR、1HNMR、13CNMR和元素分析对它们的结构进行了表征。     

丁基(三甲基硅基亚甲基)锡二芳香酸酯的合成与结构表征

采用丁基(三甲基硅基亚甲基)二氯化锡和芳香酸,在三乙胺存在下,以1:2的物质的量比进行反应,合成了9个新的混合含硅二烃基锡化合物--标题化合物.通过IR、1HNMR和13CNMR对它们的结构进行了表征.生物活性测定的初步结果表明,目标化合物Bu(Me3SiCH2)Sn(OCOC6H4NO2-p)2对肺腺癌细胞A549有较好的体外抗癌活性.     

含硅烃基氯化锡的合成及其结构表征

用四（烃硅基亚甲基）锡和四氯化锡按不同的物质的量比进行反应,合成了相应的三烃基一氯化锡、二烃基二氯化锡和一烃基三氯化锡。讨论了影响反应的主要因素,并使用高效液相色谱对反应的进程进行跟踪检测。通过^1HNMR和元素分析,确定了这些化合物的结构。生物活性试验的初步结果显示,含硅二烃基二氯化锡对肺癌细胞SPC-A-1具有较好的体外抗癌活性。     

具有生物活性的三烃基锡化合物的研究进展

主要对具有生物活性的三烃基锡化合物的研究进行回顾,其中包括不具有含硅基团的单一三烃基锡化合物、混合三烃基锡化合物,具有含硅基团的单一三烃基锡化合物、混合三烃基锡化合物,以及其它结构类型的三烃基锡化合物的生物活性研究。     

苯基-二[(三甲基硅基)亚甲基]锡芳香酸酯合成及杀螨活性

合成了两个含硅混合三烃基锡芳香酸酯：苯基-二【（三甲基硅基）亚甲基】锡苯甲酸酯、苯基-二【（三甲基硅基）亚甲基】锡对硝基苯甲酸酯，利用IR、^1H NMR、^13C NMR和元素分析表征了其结构，并进行杀螨活性测定，发现这两个化合物在200mg／L时杀螨率均超过96％，具有较强的杀螨活性。     

含硅二烃基锡二芳香羧酸酯的催化性能研究

通过酯化反应和缩醛化反应,考察了含硅二烃基锡二芳香羧酸酯在有机反应中的催化活性,讨论了催化剂用量、反应时间和溶剂等因素对催化反应的影响。实验结果表明,在酯化与缩醛化两类反应中,4种含硅二烃基锡二芳香羧酸酯均表现出良好的催化活性,其中[(CH3)3SiCH2]2Sn(OCOC6H4NO2-p)2的催化活性较高,在一定条件下酯化率可达96.3%,缩醛化率达90.6%。     

混合二烃基二氯化锡(Ⅳ)邻菲啰啉配合物的合成及结构表征

合成了5个含硅混合二烃基二氯化锡(Ⅳ)邻菲啰啉配合物,并通过IR、1HNMR和元素分析对这些配合物的结构进行了表征。结果表明,在配合物中锡原子可能为六配位结构。     

不对称二烃基二卤化锡的合成

二烃基二卤化锡是合成其他二烃基锡化合物的重要中间体，也是重要的有机合成试剂。本文主要讨论了不对称二烃基二卤化锡的合成方法。     

混合二烃基二氯化锡(Ⅳ)的合成及结构表征

利用四烃基锡化合物与浓盐酸直接混合加热反应,合成了3种混合二烃基二氯化锡(Ⅳ);通过IR、1HNMR和13CNMR的测定,对产物的结构进行了表征,探讨了反应温度、时问及浓盐酸的用量对反应产率的影响,当四烃基锡与浓盐酸的物质的量比为1:12,在92℃下反应9 min,混合二烃基二氯化锡的产率＞70%.与其他方法相比较,该方法具有操作简单、对环境污染小、产率较高等特点,符合绿色化学的要求.     

含硅三烃基锡二茂铁羧酸酯的合成及生物活性

合成了１４种含硅三烃基锡二茂铁羧酯酯,通过元素分析、ＩＲ,＾１ＨＮＭＲ表征了这些化合物的结构;化合物的生物活性实验表明,硅原子上到代基较小的化合物具有较好的生物活性。     

Synthesis and Antifungal Activity of Some Organotin(IV) Carboxylates

Six diorganotin(IV) carboxylates prepared by reacting diorganotin(IV) dichlorides with the respective silver carboxylate have been tested for antifungal activity against Aspergillus. niger, Aspergilluus flavus and Pencillium. citrinum in Sabourand dextrose broth. The compounds generally exhibit greater fungitoxicity than the diorganotin(IV) dichlorides and the carboxylic acids from which they were synthesized. In keeping with the generally accepted notion that the organotin moiety plays an important role in deciding the antifungal activity of an organotin compound, the diphenyltin(IV) compounds were more active than their di-n-butyltin(IV) analogues. However, the order of increasing fungitoxicity of the compounds parallels that of the uncomplexed carboxylic acids. The implications of the results are discussed.     

Double O,C,O-chelated diorganotin(IV) cation

The synthesis of double O,C,O-chelated diorganotin(IV) compound L₂SnBr₂ (1), where L is 2,6-(MeOCH₂)₂C₆H₃^?, the precursor for the synthesis of Sn ← O intramolecularly coordinated organotin(IV) cations is reported. Treatment of compound 1 with SnBr₄ yielded the double O,C,O-chelated diorganotin(IV) ionic pair [L₂SnBr]⁺ [SnBr₅·THF]^? (2). Both compounds 1 and 2 were characterized by ¹H, ¹³C, ¹¹⁹Sn NMR and molecular structure of compound 2 was established by X-ray diffraction.     

Antitumour Organometallics. III. In Vivo Activity of Diphenylantimony(III) and Diorganotin(IV) Dithiophosphorus Derivatives Against P388 Leukemia

Diphenylantimony(III) and diorganotin(IV) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PR'(2) (R' = Ph, OPr-i) and R(2)Sn(S(2)PR'(2))(2) (R = n-Bu, Ph, R' = Ph; R = Ph, R' = OPr-i), have been screened against P388 leukemia in mice. All the compounds showed marginal activity towards this tumor system, some of them increasing the life span of the animals with more than 20%. The best results were obtained with (di-iso-propylphosphorodithioato)diphenylantimony(III) which exhibited a T/C value of 136%, at a dose of 5 mg/kg, administered on days 1,2 and 3 after tumor transplantation.     

Tin(IV) Polymers: Part 1. Synthesis of Diorganotin Esters of Thiosalicylic Acid: X-ray Crystal Structure of Polymeric Thiosalicylatodiorganotin

Thiosalicylatodiorganotin, [R₂Sn(O₂CC₆H₄S)]_n, (R=Me (1), n-Bu (2), Ph (3), 3-Cl–PhCH₂ (4)), are prepared from thiosalicylic acid and diorganotin chlorides. All the compounds, 1–4, are characterized by elemental analysis as well as IR and ¹H-NMR spectroscopy. X-ray crystallographic analysis of the 2 and 4 shows that the structures are polymeric with neighboring diorganotin centers being linked by one O-atom of the carboxylate ligands. The carboxylate moiety is involved in coordination to one Sn atom via one O-atom while the other O-atom coordinates to the neighboring Sn atom. The mercaptotropone sulfur atom is bonded to the central Sn atom thereby establishing that Sn is five-coordinate and exists in a trigonal bipyramidal geometry.     

Interaction of Some Non-Platinum Metal Anticancer Complexes With Nucleotides and DNA and The Two-Pole Complementary Principle (TPCP) Arising Therefrom

The binding modes of some non-platinum metal anticancer complexes, Cp(2)TiCl(2), Cp(2)ZrCl(2), (CH(3))(2)SnCl(2), (C(2)H(5))(2)SnCl(2), (C(2)H(5))(2)SnCl(2)(phen) (phen=Phenanthroline) and cis-Ru(II)Cl(2)(DMSO)(3) (DMSO) (cis-RDT) with nucleotides and DNA in aqueous solution at physiological pH values were investigated by various modern techniques. 5'-dGMP with Cp(2)TiCl(2) or cis-RDT forms chelate complexes in which both N(7) and phosphate of dGMP bind to the metal center. Whereas Cp(2)ZrCl(2) and all the diorganotin compounds can bind dGMP only via the phosphate group. The investigations of the interactions between Cp(2)TiCl(2) or (C(2)H(5))(2)SnCl(2) and DNA indicate that there are two types of binding sites on DNA for Cp(2)TiCl(2), i.e., the base nitrogen rings and the phosphate group, while (C(2)H(5))(2)SnCl(2) can bind to DNA only via the phosphate group. At last, by carefully comparing and analysing the binding modes-activity relationships of the above anticancer complexes and other non-platinum and platinum anticancer complexes, a hypothesis named "Two-Pole Complementary Principle" was put forward.     

Antitumour and Immunomodulatory Effects of Cu(II) Complexes of Thiobenzyhdrazide

Thiiobenzyhdrazide (Htbh) and its Cu(II) complexes, [Cu(Htbh)2Cl2] and [Cu(tbh)2] were synthesized and characterized by various physicochemical studies. In vivo and in vitro antitumour activity of Htbh, [Cu(Htbh)2Cl2] and [Cu(tbh)2] has been tested. LD50 values were calculated for all the three compounds. It was observed that the antitumour effect of [Cu(Htbh)2Cl2] is maximum. Light microscopic study of the treated tumour mass demonstrated that certain cellular degradation, such as disappearance of mitotic figures, loss in cellular compactness, distortion of nucleus and disruption of cytoplasmic boundaries, takes place in the tumour region of complex treated mice. Further, tumour bearing mice administered with Cu(II) complexes showed reversal of tumour growth associated induction of apoptosis in lymphocytes.     

Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor,O-GlcNAcylation,Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

This article reviews the dynamic interactions of the tumour microenvironment, highlighting the roles of acetyl-CoA and melatonergic pathway regulation in determining the interactions between oxidative phosphorylation (OXPHOS) and glycolysis across the array of cells forming the tumour microenvironment. Many of the factors associated with tumour progression and immune resistance, such as yin yang (YY)1 and glycogen synthase kinase (GSK)3β, regulate acetyl-CoA and the melatonergic pathway, thereby having significant impacts on the dynamic interactions of the different types of cells present in the tumour microenvironment. The association of the aryl hydrocarbon receptor (AhR) with immune suppression in the tumour microenvironment may be mediated by the AhR-induced cytochrome P450 (CYP)1b1-driven ‘backward’ conversion of melatonin to its immediate precursor N-acetylserotonin (NAS). NAS within tumours and released from tumour microenvironment cells activates the brain-derived neurotrophic factor (BDNF) receptor, TrkB, thereby increasing the survival and proliferation of cancer stem-like cells. Acetyl-CoA is a crucial co-substrate for initiation of the melatonergic pathway, as well as co-ordinating the interactions of OXPHOS and glycolysis in all cells of the tumour microenvironment. This provides a model of the tumour microenvironment that emphasises the roles of acetyl-CoA and the melatonergic pathway in shaping the dynamic intercellular metabolic interactions of the various cells within the tumour microenvironment. The potentiation of YY1 and GSK3β by O-GlcNAcylation will drive changes in metabolism in tumours and tumour microenvironment cells in association with their regulation of the melatonergic pathway. The emphasis on metabolic interactions across cell types in the tumour microenvironment provides novel future research and treatment directions.     

Synthesis, characterization and antitumour activity of metal complexes of 5-carboxy-2-thiouracil

Metal complexes of 5-carboxy-2-thiouracil with Mn(ll), Co(ll), Ni(ll), Cu(ll), Zn(ll) and Cd(ll) ions were synthesized, characterized, and subjected to a screening system for evaluation of antitumour activity against Sarcoma-180 (S-180) tumour cells. The complexes were characterized by elemental analysis, infrared, electronic spectra, room temperature magnetic measurements and powder X-ray diffraction. The antitumour activity results indicate that some complexes have antitumour activity both in vivo and in vitro against S-180 tumour cells.     

Synthesis and biological characterisation of targeted pro-apoptotic peptide

We report herein the synthesis and in vitro assay of new, multimeric RGD-peptide conjugates for cell-targeted drug delivery. We generated a peptide scaffold comprising two functional domains, one a tumour blood vessel "homing" motif and the other a programmed cell-death-inducing peptide sequence. RGD peptides were selected to direct the molecular conjugate to alpha(V)beta(3) integrin-containing tumour cells. The pro-apoptotic (Lys-Leu-Ala-Lys-Leu-Ala-Lys)(2) peptide was found to be nontoxic outside cells, but toxic when internalized into targeted cells as it disrupted the mitochondrial membrane. The synthesis of these targeted pro-apoptotic conjugates was carried out by assembling three different units (that is, scaffold, RGD units and pro-apoptotic peptide) through chemoselective ligations. We show that one compound displays significant biological effect in alpha(V)beta(3) integrin-containing tumour cells.