Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators

Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocation methylcytosine dioxygenase 1) by specific iron chelators. Therefore, in the present work, we prepared a series of pyrrolopyrrole derivatives with hydrazide (1) or hydrazone (2–6) iron-binding groups. As a result, we determined that the basic pyrrolo[3,2-b]pyrrole derivative 1 was a strong inhibitor of the TET1 protein (IC₅₀ = 1.33 μM), supported by microscale thermophoresis and molecular docking. Pyrrolo[3,2-b]pyrroles 2–6, bearing substituted 2-hydroxybenzylidene moieties, displayed no significant inhibitory activity. In addition, in vitro studies demonstrated that derivative 1 exhibits potent anticancer activity and an exclusive mitochondrial localization, confirmed by Pearson’s correlation coefficient of 0.92.     

Spectral properties of 7H,9H-quinazolino[3,2-b]-benz[d,e]isoquinolin-7-one

The basic spectral properties (absorption and emission spectra, emission anisotropy and emission lifetime) of 7H,9H-quinazolino[3,2-b]benz[d,e]isoquinolin-7-one were measured and compared with theoretical predictions.On the basis of Perrin's and Kawski's theories the rotatory motion of the dye was also studied. The electric dipole moments in both ground and excited states and the orientation of the transition moments were obtained.     

Synthesis and properties of some 7H,9H-quinazolino-[3,2-b]benz[d,e]isoquinolin-7-one derivatives

A number of 7H,9H-quinazolino[3,2-b]benz[d,e]isoquinolin-7-one derivatives containing chlorine atoms, methoxy, nitro or amino groups at the 11 or 12 position of the molecule skeleton have been synthesised.The structure of the dyes obtained has been confirmed by elemental analysis, as well as by i.r. and n.m.r. spectroscopy. Electronic spectra in the visible range have also been recorded and the effect of the character of the substituents on the colour has been analysed.     

Synthesis and Dyeing Examinations of 7H, 9H-Quinazolino [3,2-b] benz [d,e] isoquinolin-7-one

The synthesis and application of a representative compound of the new group of disperse dyes derived from 7H,9H-quinazolino[3,2-b] benz[d, e] isoquinolin-7-one (II) have been investigated. The MS, IR and NMR spectra of compound (II) are analysed, and its dyeing and colour properties are compared with 7H-benzimidazo-[2,1-a] benz [d.e] isoquinolin-7-one (I).     

5-羟基-1,3,4-噻二唑[3,2-a]并嘧啶-7-酮衍生物的绿色合成

为了寻找干扰嘌呤核酸代谢的抗肿瘤新药,设计和合成了嘌呤生物碱的类似物。以2-氨基-1,3,4-噻二唑、丙二酸与三氯氧磷为原料,经过关环,偶合等反应合成了9种5-羟基-1,3,4-噻二唑[3,2-a]并嘧啶-7-酮衍生物,通过元素分析、IR、1 H NMR和质谱分析确定了其结构。     

Intercluster porous nanocomposites from combination of [AlO4Al12(OH)24(H2O)12]7+ cation and Anderson-type [Al1? x Cr x Mo6O24H6]3? anion: XRD, TG-DTA, SEM-EDAX and EPR studies

The synthesis of intercluster porous nanocomposites obtained from polyoxometallate compounds such as the [AlO₄Al₁₂(OH)₂₄(H₂O)₁₂]⁷⁺ cation (named Al₁₃) and the Anderson-type [Al_1−x Cr _x Mo₆O₂₄H₆]³⁻ anion (named Al_1−x Cr _x Mo₆) has been performed in order to study the interaction between the two cluster ions, the stability of the XMo₆ planar configuration, the products obtained after thermal treatment, the structure and the local symmetry of the Cr³⁺ species. Chemical, thermal, structural and spectroscopic characterizations of the original and thermally treated phases have been followed by different techniques such as TG-DTA, XRD, SEM-EDAX, and mainly by EPR. All the results have shown that the structure of the intercluster nanocomposites (Al₁₃)(Al_1−x Cr _x Mo₆)₂ precursors is similar to that reported by Son et al. for the chromium-free (Al₁₃)(AlMo₆)₂ intercluster nanocomposite [Son et al., J. Am. Chem. Soc. 122 (2000) 7432]. After thermal treatment in air at several temperatures of the (Al₁₃)(Al_1−x Cr _x Mo₆)₂ nanocomposites the following phases have been observed and characterised: (i) at 400 °C an amorphous phase containing dispersed Cr³⁺ ions; (ii) at 700 °C a crystalline phase corresponding to Cr₂(MoO₄)₃/Al₂(MoO₄)₃ solid solutions; (iii) at 950 °C α-Al₂O₃/Cr₂O₃ solid solutions with a random dispersion of the Cr³⁺ ions.     

5-亚氨基-7-氧代-6-芳基偶氮-1,3,4-噻二唑[3,2-a]并嘧啶衍生物的绿色合成

合成了5种新的5-亚氨基-7-氧代-6-芳基偶氮-1,3,4-噻二唑[3,2-a]并嘧啶衍生物,通过元素分析、IR、1HNMR和质谱分析确定了其结构.     

N-羟甲基-2,3-二丁硫基四硫富瓦烯并[6,7-c]吡咯的合成

从4,5-二丁硫基-1,3-二硫杂环戊二烯-2-酮和N-对苯磺酰基-2-硫代-1,3-二硫杂环戊二烯并[4,5-c]吡咯出发,经交叉偶联、去保护得2,3-二丁硫基四硫富瓦烯并[6,7-c]吡咯(4)。化合物4在碱存在下与甲醛水溶液(37%)反应生成N-羟甲基化的产物。用核磁共振氢谱研究了标题化合物在不同极性溶剂中的偶合行为。     

AMAT的硝化反应及其MNCIO的合成

2－乙酰基－7－甲胺基Zhou酮（AMAT）（1）与硝酸反应，得到2－乙酰基－7－基胺基－4－硝基恶酮（2）。谷物化合物2在碱性条件下水解，得到3－乙酰基－5－硝基Zhou酚酮（3）。化合物3与盐酸羟胺反应，得到3－甲基－5－硝基－8H－环庚并[d]异恶唑－8－酮（MNCIO）（4）。它们的结构均经红外光谱、核磁共振谱得到证实。其中化合物2是未见文献报道的新化合物。     

8-氨基苯并[4,5]呋喃并[3,2-d]嘧啶类衍生物的合成与结构表征

以5-硝基水杨醛为原料,经过氰基化、醚化、两次成环、氯代等反应合成11个新型的8-位氨基取代苯并[4,5]呋喃并[3,2-d]嘧啶类化合物,利用1HNMR、13CNMR、IR和MS对其结构进行了表征,并对该反应条件进行了探索,得出最优的反应条件。     

噻唑并[3,2-b][1,2,4]三唑酮衍生物的合成及抗癌活性研究

以3,4,5-三甲氧基苯甲酸为原料,经过Claisen缩合等反应设计合成一系列新的噻唑并[3,2-b][1,2,4]三唑-6-酮稠杂环衍生物并测定其体外抗肿瘤活性。目标化合物经~1HNMR、~(13)CNMR和高分辨质谱等表征后,在He La、HCT116、BEL-7402及L-02细胞中用MTT法测定其抑制细胞增殖的程度,并初步判断化合物的体外抗癌活性。结果表明,与临床常用药顺铂(DDP)相比,多数化合物具有抑制肿瘤细胞增殖活性。其中,5-(4-苄氧基苯亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮、5-(4-乙酰氧基苯亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮、5-(α-呋喃亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮和5-(α-噻吩亚甲基)-2-(3,4,5-三甲氧基苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮对HCT116等3种癌细胞的抑制率高于正常细胞L-02,且对癌细胞有选择性抑制作用,而对正常细胞无毒性,具有良好的后续研究价值。5-(4-氟苯亚甲基)-2-(3,4,5-三羟苯基)噻唑并[3,2-b][1,2,4]三唑-6(5H)-酮对BEL-7402等细胞的抑制率有大幅度提高,但对L-02正常细胞的毒性更大。     

苯并呋喃[3,2-d]嘧啶类衍生物生物活性及研究进展

阐述了苯并呋喃[3,2-d]嘧啶类化合物在抗菌、抗炎、抗癌、降血糖及抑制血小板聚集和促进长时记忆等方面的应用,对苯并呋喃[3,2-d]嘧啶类衍生物的合成方法进行总结,并且对这类化合物的发展趋势进行了分析。     

An asymmetrically substituted dithieno[3,2-b:2',3'-d]pyrrole organic small-molecule hole-transporting material for high-performance perovskite solar cells

Hole-transporting materials play a vital role in terms of the performance of perovskite solar cells (PSCs). The dithieno[3,2-b:2',3'-d]pyrrole (DTP), an S,N-heterocyclic building block, has been proved to be desirable for molecular design of hole-transporting materials in PSCs. We developed an asymmetrically substituted DTP small-molecule (JW12) and a reference compound (JW11). The asymmetrical structure of JW12 leads to different absorption properties and electron distribution. The device in a planar n-i-p architecture using JW12 shows a much higher PCE (18.07%) than that based on JW11 (15.46%), which is also better than the device based on spiro-OMeTAD (17.47%). We hope our research can provide a new perspective in molecular design of organic HTMs for perovskite solar cells.     

Meso-四甲基-meso-四对氨苯基杯[4]吡咯的合成及表征

以吡咯和对氨基苯乙酮为原料合成了meso-四甲基－meso-四对氨苯基杯[4]吡咯，研究了反应时间，温度、浓度等对收率的影响，其结构通过红外光谱，核磁共振，电喷雾质谱和元素分析进行了确证。     

9-硝基-9-氮杂双环[3.3.1]壬烷-2,6-二醇二硝酸酯的合成与表征

以环辛二烯为原料,经环氧化、胺化成环、硝化等合成了一种新型含能材料9-硝基-9-氮杂双环[3.3.1]壬烷-2,6-二醇二硝酸酯,采用NMR、IR、元素分析对其结构进行了表征;利用热重分析和差示扫描量热法对其热性能进行了分析;利用Kamlet-Jacobs经验公式对其爆轰性能进行了理论计算;研究了硝化反应过程中反应时间、反应温度和物料配比等因素对收率的影响。结果表明,硝酸用量为7倍摩尔当量时,在30℃下反应3h,目标产物收率为83%。9-硝基-9-氮杂双环[3.3.1]壬烷-2,6-二醇二硝酸酯熔点为120℃,起始分解温度为150℃,放热峰温为192℃,表明其具有较好的热稳定性。其爆速、爆压、密度的理论计算值分别为7 580m/s、23.82GPa和1.61g/cm3,有望应用于炸药及推进剂配方中。     

Base induced [1,2]- and [3,2]-rearrangements of N-(2-Thenyl)-N-benzyldimethylammonium ion

The title compound 4 underwent Sommelet and Stevens rearrangements induced by a number of bases. Ionization of the thenyl methylene group of 4 to the corresponding ylid 10 was the prevalent process, yielding subsequently N-[2-(2′-thienyl)-2-phenethyl]dimethylamine 12 and N-[α-(o-tolyl)-2-thenyl]-dimethylamine 13 . The strong trend of the 2-thenyl ylids to produce large relative amounts of the Sommelet amine was confirmed. Minor products are N-[2-(2′-thienyl)-1-phenethyl]dimethylamine 15 and N-[α-phenyl-2-(3-methylthienyl)]dimethylamine 16 derived from the benzyl ylid 11 .     

呋喃并[3,2-g]色满类化合物的合成及抗肿瘤活性研究

为了发现新型选择性雌激素受体调节剂,以雷洛昔芬为先导化合物,利用生物电子等排原理以及拼合原理,将雷洛昔芬结构中的苯并噻吩环替换成呋喃并[3,2-g]色满骨架,并进行结构优化,考虑到目标化合物合成的可行性等因素,设计出2-芳酰基-3-芳基呋喃并[3,2-g]色满类化合物作为目标化合物。以7-羟基色满为原料,经过酯化反应和Fries重排后得到6-(4-甲氧基苯甲酰基)-7-羟基色满,进而与取代的α-卤代苯乙酮缩合得关键中间体2-芳甲酰基-3-(4-甲氧基苯基)呋喃并[3,2-g]色满,脱甲基后再与不同氯乙基胺类化合物进行Williamson反应得到目标化合物。所有的10个目标化合物均未见文献报道,其结构经ESI-MS和1H NMR确证。采用MTT法对目标化合物体外抗肿瘤活性进行初步筛选,结果表明,目标化合物7d对人乳腺癌细胞MCF-7、人骨肉瘤细胞U2OS-EGFP-4A12G和人卵巢癌细胞SKOV3具有显著的抑制活性,具有进一步研究价值。     

Poly(dihexadecyl-4H-cyclopenta[2,1-b:3,4-b′]dithiophene) film formation by cyclic voltammetry: dependence of the optical properties and morphology on the thickness

The voltammetric, morphologic and spectral properties of poly(dihexadecyl-4H-cyclopenta[2,1-b:3.4-b′]dithiophene), synthesised on ITO electrode in acetonitrile/dichloromethane mixed solvent by cyclic voltammetry, strongly depend on the film thickness. The polymerisation occurs through two successive steps: the electrode covering and a further growing of the film on the polymer coated electrode. The rate of the film growing is higher in acetonitrile-rich solvent and is a linear function of the monomer concentration during both the electrode covering and the subsequent growing step.     

Synthesis of 2,3,6,8-Tetrahydroxybenzofuro[3,2-b][1]benzopyrylium Chloride (Riccionidin A)

The liverwort pigment riccionidin A ( 1 ) was synthesized in a single preparative step from simple starting materials by a double condensation reaction.     

Kinetic study of 3,6-dimethylthieno[3,2-b]thiophene electropolymerisation

A systematic investigation was carried out by means of cyclic voltammetry, chronoamperometry and chronopotentiometry on 3,6-dimethylthieno[3,2-b]thiophene (DMTT) electropolymerisation on vitreous carbon in acetonitrile (ACN) containing 0.1 M LiClO₄. The electrochemical doping–undoping process was reversible and the coulombic efficiency over a charge–discharge cycle was ca. 100%. The electropolymerisation mechanism was unchanged by the presence of methyl groups. When an aluminium electrode was used, poly(DMTT) deposition could only be performed in the potentiostatic mode. In this case, electropolymerisation hindered the pitting process on Al, which was initiated in the early stages of anodisation.