Design, synthesis and biological activity of new CDK4-specific inhibitors, based on fascaplysin

We present the design, synthesis, and biological activity of three classes of tryptamine derivatives, which are non-planar analogues of the toxic anti-cancer agent fascaplysin. We show these compounds to be selective inhibitors of CDK4 over CDK2, the most active compound has an IC50 for the inhibition of CDK4 of 6 microM.     

New fascaplysin-based CDK4-specific inhibitors: design, synthesis and biological activity

The first biologically active non-planar analogues of the toxic anti-cancer agent, fascaplysin, have been produced; we present the design, synthesis and biological activity of three tryptamine derivatives.     

双乙酰二茂铁缩肼基二硫代甲酸甲酯Schiff碱的合成、晶体结构和生物活性(英文)

用双乙酰二茂铁和肼基二硫代甲酸甲酯为起始原料,制备了含二茂铁的Schiff碱配体[(CH3)SSCNHN=C(CH3)(C5H4)]2Fe.利用元素分析以及红外光谱和单晶X射线衍射分析了产物的组成、化学特征及晶体结构,并测定了其生物活性.结果表明,标题化合物对Ec9706食管癌细胞株具有适度的生长抑制活性.     

水杨醛缩2-芴胺席夫碱的合成、晶体结构及生物活性

芴在煤焦油中的含量为1%～2%,全国每年可从中提取1.4万吨芴.芴是一种带有荧光的片状化合物,作为一种新型的发光材料主要用于制备芴基金属化合物、有机光导体、树脂、染料、Ziegler-Natta催化剂的给电子体等.     

Synthesis,characterization, crystal structure,and biological activity of the copper complex

This work reports the synthesis and biological activity of the copper complex with 2–thenoyltrif-luoroacetone (HTTA). The complex was characterized by elemental analysis, infrared spectroscopy, and thermogravimetric analysis. The crystal structure was determined by single-crystal X-ray diffraction. The complex exists as a parallelogram with four coordination sites occupied by the carbonyl oxygen atoms from HTTA. The antibacterial activity test shows that the complex exhibits better antibacterial ability against Escherichia coli and Staphylociccus aureus (MIC were about 180, 150 μg/ml, respectively) and can be considered as broad-spectral antimicrobial. The antitumor activity of the copper(II) complex is tested by methyl thiazolyl tetrazolium assays against human Leukemia cells K562. The copper(II) complex exhibits potent antitumor effects against K562 cell lines. The IC₅₀ value of the complex is about 0.01 μg/ml. The research shows that the complex can inhibit K562 tumor cell growth and generation and induce apoptosis. The inhibition ratio is accele by increasing the dosage and has a significant positive correlation with medication dosage.     

Synthesis,crystal structure,and photo/electrocatalytic properties of a 1D chain based on monocobalt-substituted arsenotungstates

A chain based on the Keggin polyoxoanions, (H₂bipy)₂(Hbipy) [AsW₁₁CoO₃₉]·H₂O (bipy = 4,4′-bipyridine) (1) has been hydrothermally synthesized and characterized by elemental analysis, IR, UV, TG, and single-crystal X-ray diffraction. In 1, substituted cobalt atoms share half occupancy sites with two W atoms on two asymmetric positions of opposite W₃O₁₃ trimers forming mono-substituted Keggin arsenotungstate. The Keggin clusters of two different arrays are alternately connected to generate unique wave-like chains in –A–B–A–B– ways via Co–O–W bridge. Compound 1 exhibits bifunctional electrocatalytic behavior for oxidation of ascorbic acid (AA) and reduction of hydrogen peroxide (H₂O₂), and good degradation ability for three typical dyes under UV light.     

Synthesis,characterisation, crystal structure and biological activity of metal(II) complexes with theophylline

Three metal complexes with empirical formulae [Mn(theop)₂(H₂O)₄] (1), [Co(theop)₂(H₂O)₄] (2), [Ni(theop)₂(H₂O)₄] (3), (where: theop?=?theophylline) were synthesized and characterized by elemental analysis, FTIR- spectroscopy and thermal decomposition techniques. Their crystal structures were determined by single crystal Xray diffraction analysis. Complexes are isomorphous and crystallise in the monocyclic space group P21/c. Their thermal behavior was studied by TGA methods under non-isothermal condition in air. Upon heating all compounds decompose progressively to metal oxides, which are the final products of pyrolysis. Furthermore, antimicrobial and antioxidant activity of the complexes was examined.     

Synthesis, crystal structure and biological activity of a novel anthranilic diamide insecticide containing allyl ether

In search of environmentally benign insecticides with high activity, low toxicity and low residue, a series of novel anthranilic diamides containing allyl ether were designed and synthesized. All the compounds were characterized by ¹H NMR spectroscopy, HRMS or elemental analysis. The single crystal structure of 18e was determined by X-ray diffraction. The insecticidal activities of the new compounds were evaluated. The results showed that some compounds exhibited excellent insecticidal activities against Lepidoptera pests. Among this series compounds, 18l showed 100 % larvicidal activity against Mythimna separate Walker and Plutella xylostella Linnaeus at the test concentration.     

Structural determinants of CDK4 inhibition and design of selective ATP competitive inhibitors

A number of selective inhibitors of the CDK4/cyclin D1 complex have been reported recently. Due to the absence of an experimental CDK4 structure, the ligand and protein determinants contributing to CDK4 selectivity are poorly understood at present. Here, we report the use of computational methods to elucidate the characteristics of selectivity and to derive the structural basis for specific, high-affinity binding of inhibitors to the CDK4 active site. From these data, the hypothesis emerged that appropriate incorporation of an ionizable function into a CDK2 inhibitor results in more favorable binding to CDK4. This knowledge was applied to the design of compounds in the otherwise CDK2-selective 2-anilino-4-(thiazol-5-yl)pyrimidine pharmacophore that are potent and highly selective ATP antagonists of CDK4/cyclin D1. The findings of this study also have significant implications in the design of CDK4 mimic structures based on CDK2.     

Synthesis,spatial structure,and biological activity of 1-AZA-4-oxabicyclo[4.1.0]heptan-5-ones

It has been found that the reaction of - and -amino alcohols with methyl 1,2-dibromopropionate results in the formation of esters of 1-(hydroxyalkyl)aziridine-2-carboxylic acids or 1-aza-4-oxabicyclo[4.1.0]pentan-5-ones, depending on the nature of the original reactants. An x-ray structural analysis of this new bicyclic system has been carried out. The hepatoprotector activity of the new compounds has been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1349–1354, October, 1984.     

Synthesis,crystal structure,and biological activity of a nickel(II) complex of 2-acetylpyridine N(4)-methylthiosemicarbazone

Nickel complex formulated as Ni(L)₂ (L = monodeprotonated ligand corresponding to 2-acetylpyridine N(4)-methylthiosemicarbazone, HL) has been synthesized and characterized by elemental analysis, IR spectra, and single-crystal X-ray diffraction. The complex consists of discrete monomeric molecules with octahedral nickel(II) with two anionic 2-acetylpyridine N(4)-methylthiosemicarbazones as NNS tridentate ligands coordinated to nickel via the pyridine nitrogen, azomethine nitrogen, and sulfur. Hydrogen bonds link the different components to stabilize the crystal structure. Biological studies, carried out in vitro against bacteria, fungi, and the K562 leukemic cell line have shown that the free ligand and complex show distinct differences in biological activity.     

新型手性单胺氧化酶选择性抑制剂的设计、合成与生物活性研究

本文以取代的手性苯乙胺为原料,设计合成了4种新型叔胺盐酸盐化合物.通过NMR,IR和MS等表征方法对所合成目标产物的结构进行确定.在生物活性方面,首先通过CCK-8法测定4种化合物对正常细胞增殖的影响,实验结果表明:部分化合物对小鼠成纤维细胞L929表现出一定的细胞毒性.酶的选择性实验说明R构型影响小分子对单胺氧化酶(MAO)的选择性抑制活性,另一方面取代基的给电子能力也会对酶的活性有影响.     

Synthesis,crystal structure and biological activity of the nickel(II) complex of 2,6-diacetylpyridinedihydrazone

A complex of Ni^II with 2,6-diacetylpyridinedihydrazone (L) towards nickel(II) has been prepared and characterized by means of elemental analyses, IR, electronic spectra and single crystal X-ray analyses. [NiL₂](NO₃) was crystallized in the tetragonal space group P-4 21 c. The complex exhibits the expected coordination sphere with six nitrogen atoms coordinated to the central Ni^II with a deformation from pseudo-octahedral geometry. Antimicrobial activities of the ligand and its complex were investigated.     

Synthesis and antimycobacterial activity of some beta-carboline alkaloids

In view of the attributed medicinal properties of beta-carboline alkaloids, some new O-acyl derivatives of beta-carboline alkaloid--harmol, were prepared and tested for possible antimycobacterial activity against Mycobacterium tuberculosis H37Rv.     

Synthesis and crystal structure of isotactic poly-4-phenyl-1-butene

Poly-(4-phenyl-1-butene) was prepared by using a titanium tetrachloride–triethyl-aluminum catalyst. The crystalline polymer melts at 158°C. Double orientation could not be obtained but all the reflections on the x-ray fiber diagram can be indexed on the basis of an hexagonal cell (a = 20.8 A., c (fiber repeat) = 6.61 A.). However the crystal structure proposed does not belong to an hexagonal space group but to the monoclinic (pseudo-orthorhombic) space group Pa (a = 10.4 A., b = 18.0 A., c = 6.61 A.). The 3₁ helix, common to systems of this type, is consistent with an isotactic (not syndiotactic) configuration for the polymer chain.     

Synthesis, structure proof, and biological activity of epothilone cyclopropanes

[structure--see text] A semisynthetic route to epothilone cyclopropanes from epothilones A and B is described. Of significance, the deoxygenation of the 12, 13-epoxide to give the corresponding olefin was achieved with high efficiency. The title compounds (8, 9) were active in both tubulin polymerization and cytotoxicity assays, which is in direct contrast to a previously published report. These results provide further evidence that the role of the 12,13-epoxide of epothilones is largely conformational and argue against some of the current pharmacophore models.