氨基二硫代甲酸酯类化合物生物活性研究进展

氨基二硫代甲酸酯类化合物由于其独特的分子结构,使其具有明显的抗肿瘤、抗菌、抗氧化以及杀虫等多种生物活性,已经成为近年来药物化学领域研究的重点。 本文评述了近年来文献报道的氨基二硫代甲酸酯类化合物以及它们的主要生物活性,并对其今后的发展方向、应用前景做出展望。     

新型18β-甘草次酸氨基二硫代甲酸酯衍生物的合成及抗癌活性研究

以18β-甘草次酸为原料首先经简单酰胺化反应方便地得到18β-甘草次酸哌嗪,再与二硫化碳、碳酸钾以及不同结构卤代烃"一锅煮"法快速、高效地合成了10种含氨基二硫代甲酸酯结构的新型甘草次酸酰胺类衍生物,通过IR,1H NMR,13C NMR和HR-MS对所有新化合物进行了结构确证;并以四甲基偶氮唑盐比色法(MTT)法评价了该类化合物对人肝癌细胞株SMMC-7721的细胞毒活性.初步生物活性研究结果表明,该类化合物具有明显的抑制人肝癌细胞增殖、诱导其凋亡的细胞毒活性,给药72 h,半抑制浓度IC50最优值仅为14.42μg/mL.     

Unusual reactivity of tantalum pentakis(dimethylpyrazolate) with CS2: scission of the C=S bond and formation of dmpz3CS– ligand

The reaction beetwen tantalum pentakis(3,5-dimethyl-pyrazolate) and CS₂ afforded novel complex [Ta(=S)(dmpz)₂{(dmpz)₃CS}]. In this reaction the molecule of CS₂ undergoes scission with the migration of one sulfide to the tantalum atom while three pyrazolate residues migrate to carbon with the formation of unusual (dmpz)₃CS^– ligand. The structure of the product was established by X-ray diffraction.     

Synthesis,Structure and Light‐Harvesting Properties of Some New Transition‐Metal Dithiocarbamates Involving Ferrocene

Nine new transition‐metal dithiocarbamates involving ferrocene (Fc), namely, [M(FcCH₂Bzdtc)₂] (M=Ni^II ( 1 ), Cu^II ( 2 ), Cd^II ( 3 ), Hg^II ( 4 ), Pd^II ( 5 ), Pt^II ( 6 ) and Pb^II ( 7 ); Bzdtc=N‐benzyl dithiocarbamate) and [M(FcCH₂Bzdtc)₃] (M=Co^II ( 8 ) and UO₂^VI ( 9 )), have been synthesised and characterised by micro analyses, IR spectroscopy, ¹H and ¹³C NMR spectroscopy, and in three cases by single‐crystal X‐ray analysis. The peak broadening in the ¹H spectrum of the copper complex indicates the paramagnetic behaviour of this compound. A square‐planar geometry around the nickel and copper complexes and distorted linear geometry around the mercury complex have been found. The latter geometry is attributed to the bulkiness of the methylferrocenyl and benzyl groups. The observed single quasi‐reversible cyclic voltammograms for complexes 2 , 8 and 9 indicate the stabilisation of a metal centre other than Fe in their characteristic oxidation state. These complexes have been used as a photosensitiser in dye‐sensitised solar cells.     

Gold(III) to Ruthenium(III) Metal Exchange in Dithiocarbamato Complexes Tunes Their Biological Mode of Action for Cytotoxicity in Cancer Cells

Malignant tumors have affected the human being since the pharaoh period, but in the last century the incidence of this disease has increased due to a large number of risk factors, including deleterious lifestyle habits (i.e., smoking) and the higher longevity. Many efforts have been spent in the last decades on achieving an early stage diagnosis of cancer, and more effective cures, leading to a decline in age-standardized cancer mortality rates. In the last years, our research groups have developed new metal-based complexes, with the aim to obtain a better selectivity for cancer cells and less side effects than the clinically established reference drug cisplatin. This work is focused on four novel Au(III) and Ru(III) complexes that share the piperidine dithiocarbamato (pipe-DTC) as the ligand, in a different molar ratio. The compounds [AuCl₂(pipeDTC)], [Au(pipeDTC)₂]Cl, [Ru(pipeDTC)₃] and β-[Ru₂(pipeDTC)₅] have been synthesized and fully characterized by several chemical analyses. We have then investigated their biological properties in two different cell lines, namely, AGS (gastric adenocarcinoma) and HCT116 (colon carcinomas), showing significant differences among the four compounds. First, the two gold-based compounds and β-[Ru₂(pipeDTC)₅] display IC₅₀ in the µM range, significantly lower than cisplatin. Second, we showed that [AuCl₂(pipeDTC)] and β-[Ru₂(pipeDTC)₅]Cl drive different molecular mechanisms. The first was able to induce the protein level of the DNA damage response factor p53 and the autophagy protein p62, in contrast to the second that induced the ATF4 protein level, but repressed p62 expression. This study highlights that the biological activity of different complexes bringing the same organic ligand depends on the electronic and structural properties of the metal, which are able to fine tune the biological properties, giving us precious information that can help to design more selective anticancer drugs.     

The in vitro antifungal activity of some dithiocarbamate organotin(IV) compounds on Candida albicans— a model for biological interaction of organotin complexes

The in vitro antifungal activity of the dithiocarbamate organotin complexes [Sn{S₂CN(CH₂)₄}₂Cl₂] ( 1 ), [Sn{S₂CN(CH₂)₄}₂Ph₂] ( 2 ), [Sn{S₂CN(CH₂)₄}Ph₃] ( 3 ), [Sn{S₂CN(CH₂)₄}₂n‐Bu₂] ( 4 ), [Sn{S₂CN(CH₂)₄}Cy₃] {Cy = cyclohexyl} ( 5 ), [Sn{S₂CN(C₂H₅)₂}₂Cl₂] ( 6 ), [Sn{S₂CN(C₂H₅)₂}₂Ph₂] ( 7 ), [Sn{S₂CN(C₂H₅)₂}Ph₃] ( 8 ), [Sn{S₂CN(C₂H₅)₂}₃Ph] ( 9 ) and [Sn{S₂CN(C₂H₅)₂}Cy₃] ( 10 ) has been screened against Candida albicans (ATCC 18804), Candida tropicalis (ATCC 750) and resistant Candida albicans collected from HIV‐positive Brazilian patients with oral candidiasis. All compounds exhibited antifungal activities and complexes 3 and 8 displayed the best results. We have investigated the effect of compounds 1–10 on the cellular activity of the yeast cultures. Changes in mitochondrial function have not been detected. However, all drugs reduced ergosterol biosynthesis. Preliminary studies on DNA integrity indicated that the compounds do not cause gross damage to yeast DNA. The data suggest that these compounds share some mechanisms of action on cell membranes similar to that of polyene but not with azole drugs, normally used in Candida infections. Copyright © 2008 John Wiley & Sons, Ltd.     

Ruthenium(II/III)‐Based Compounds with Encouraging Antiproliferative Activity against Non‐small‐Cell Lung Cancer

Hereby we present the synthesis of several ruthenium(II) and ruthenium(III) dithiocarbamato complexes. Proceeding from the Na[trans‐Ru^III(dmso)₂Cl₄] ( 2 ) and cis‐[Ru^II(dmso)₄Cl₂] ( 3 ) precursors, the diamagnetic, mixed‐ligand [Ru^IIL₂(dmso)₂] complexes 4 and 5 , the paramagnetic, neutral [Ru^IIIL₃] monomers 6 and 7 , the antiferromagnetically coupled ionic α‐[Ru^III₂L₅]Cl complexes 8 and 9 as well as the β‐[Ru^III₂L₅]Cl dinuclear species 10 and 11 (L=dimethyl‐ (DMDT) and pyrrolidinedithiocarbamate (PDT)) were obtained. All the compounds were fully characterised by elemental analysis as well as ¹H NMR and FTIR spectroscopy. Moreover, for the first time the crystal structures of the dinuclear β‐[Ru^III₂(dmdt)₅]BF₄ ? CHCl₃ ? CH₃CN and of the novel [Ru^IIL₂(dmso)₂] complexes were also determined and discussed. For both the mono‐ and dinuclear Ru^II and Ru^III complexes the central metal atoms assume a distorted octahedral geometry. Furthermore, in vitro cytotoxicity of the complexes has been evaluated on non‐small‐cell lung cancer (NSCLC) NCI‐H1975 cells. All the mono‐ and dinuclear Ru^III dithiocarbamato compounds (i.e., complexes 6 – 10 ) show interesting cytotoxic activity, up to one order of magnitude higher with respect to cisplatin. Otherwise, no significant antiproliferative effect for either the precursors 2 and 3 or the Ru^II complexes 4 and 5 has been observed.     

The addition reaction of acrylonitrile and methylacrylate toN-(5R-1,3,4-thiadiazol-2-yl)dithiocarbamates

A new type of dithiocarbamic acid derivatives,S-(2-X-ethyI) ethers ofN-(5R-1,3,4-thiadiazol-2-yl)-dithiocarbamic acids (X = CN, COOMe), has been synthesized by the reaction of sodiumN-(1,3,4-thiadiazol-2-yl) dithiocarbamates with acrylonitrile and methylacrylate.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 749–750, April, 1994.     

Thermal decomposition of transition metal dithiocarbamates

Transition metal dithiocarbamate complexes, [M(S₂CN(C₂H₅)(CH₂CH₂OH)] (M=Co, Ni, Cu, Zn and Cd) have been prepared and characterized by elemental analysis and infrared spectra. Thermal decomposition of all the complexes occurs in two or three stages. The first stage in all the complexes is always fast with 65-70% mass loss. In all cases the end product is metal oxide except in the case of cobalt complex which gives Co metal as an end product. During decomposition of copper complex, first CuS is formed at ~300°C which is converted into CuSO₄ and finally CuO is formed. However, decomposition in helium atmosphere yields CuS. SEM studies of transition metal dithiocarbamates reveal needle shape crystalline phase at room temperature and formation of metal sulphide/oxide at higher temperatures. The activation energy varies in a large range of 33.8-188.3 kJ mol^-1, being minimum for the Cu complex and maximum for the Zn complex possibly due to d ¹⁰ configuration. In the case of Ni, Zn and Cd complexes the order of reaction is two suggesting bimolecular process involving intermolecular rearrangement. However, in other cases it is a unimolecular process. Large negative values of ΔS ^# for all the complexes suggest that the decomposition process involves rearrangement. This revised version was published online in July 2006 with corrections to the Cover Date.     

Organotin(IV) azepane dithiocarbamates: Synthesis and characterization of the first organotin(IV) complexes with seven-membered cyclic dithiocarbamates

Abstract

We report the synthesis and spectroscopic characterization of the first organotin(IV) complexes with cyclic seven-membered dithiocarbamate ligands: the azepane-1-carbodithioate and the homopiperazine-1,4-bis-carbodithioate with two different organotin entities, di-n-butyltin and tri-cyclohexyltin: [(C₄H₉)₂Sn{S₂CN(CH₂)₆}₂] (3), [(C₆H₁₁)₃Sn{S₂CN(CH₂)₆}] (4), and [(C₆H₁₁)₃Sn}₂ (μ-S₂CN(C₅H₁₀)NCS₂)] (5). Compounds (3–5) are air-stable both in solid-state and in solution, and were characterized by elemental analyses, IR, FAB⁺–MS, and multinuclear NMR (¹H, ¹³C, and ¹¹⁹Sn) spectroscopy. Their molecular structures were unambiguously established by single-crystal X-ray diffraction studies. The geometrical arrangement around the tin atom can be described as distorted octahedral for (3) and distorted trigonal bipyramid for (4) and (5). The coordination mode for both ligands is considered as asymmetric bidentate, as happens in other organotin(IV) dithiocarbamates. Furthermore, (4) and (5) do not exhibit intermolecular secondary interactions, while (3) presents intermolecular interactions between the tin and a sulfur atom with the reciprocally neighboring molecule, giving rise to a zig-zag polymeric structure.