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961.
Hue Thi Buu Bui Phuong Hong Nguyen Quan Minh Pham Hoa Phuong Tran De Quang Tran Hosun Jung Quang Vinh Hong Quoc Cuong Nguyen Quy Phu Nguyen Hieu Trong Le Su-Geun Yang 《Molecules (Basel, Switzerland)》2022,27(7)
Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC50 values of 3.4–37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC50 value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (−7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11. 相似文献
962.
Olha Dzydzan Iryna Brodyak Paulina Strugaa-Danak Angelika Strach Alicja Z. Kucharska Janina Gabrielska Natalia Sybirna 《Molecules (Basel, Switzerland)》2022,27(7)
Although extracts are broadly used in order to support the treatment of numerous diseases, only in a limited number of cases is the process of applying and establishing their mechanisms of action scientifically analyzed. Fruits of Cornelian cherry are an abundant source of iridoids, anthocyanins, flavonols and phenolic acids. The aim of the present study was to evaluate the in vitro bioactivity of red and yellow Cornelian cherry fruits’ extracts. The biological potential of extracts, in a broad sense, involved antioxidant activity in relation to phosphatidylcholine liposomes, inhibitory ability against α-glucosidase and acetylcholinesterase enzymes, as well as interactions with human serum albumin. Studies showed that both extracts were more effective in protecting liposome membranes against free radicals produced by AAPH in an aqueous environment due to the fact that they can be better eliminated by the hydrophilic components of the extracts than those produced by UVB radiation. Extracts exhibited inhibitory activity against acetylcholinesterase and α-glucosidase, wherein loganic acid extract showed noncompetitive inhibition of the enzyme. Moreover, extracts binded to albumin mainly through hydrogen bonds and van der Waals forces. Taken together, red and yellow cherry fruits’ extracts exhibit diverse biological properties and can be exploited as a source of natural therapeutic agents. 相似文献
963.
Macrocyclic chemistry has been extensively developed over the past several decades. In fact, the architecture of new macrocyclic models has undergone exponential growth to offer molecules with specific properties. In this context, an attempt is made in this study to provide an overview of some synthetic methods allowing the elaboration of N-heterocycles containing macrocycles (imidazole, triazole, tetrazole, and pyrazole), as well as their applications in the complexation of metal cations or as pharmacological agents. 相似文献
964.
A series of new thiophene-containing triaryl pyrazoline derivatives, 3a–3t, were synthesized and evaluated regarding PI3K inhibition activity and anti-tumor potency based on a trial of introducing significant moieties, including pyrazoline and thiophene, and simplifying the parallel ring structures. Most of the tested compounds indicated potent PI3K inhibitory potency, with this series of compounds showing more potency for PI3Kγ than PI3Kα. The top hit 3s seemed more potent than the positive control LY294002 on inhibiting PI3Kγ (IC50 values: 0.066 μM versus 0.777 μM) and more selective from PI3Kα (Index values: 645 versus 1.74). It could be inferred that the combination of para- and meta-, as well as the modification of the electron-donating moieties, led to the improvement in potency. The anti-proliferation inhibitory activity and the enzymatic inhibition potency indicated consistent tendencies. The top hit 3s could inhibit the phosphorylation of Akt by inhibiting PI3K through the PI3K-Akt-mTOR pathway. The molecular docking simulation indicated that the binding pattern of 3s into PI3Kγ was preferable than that of PI3Kα, with more hydrogen bond, more π-involved interactions, and fewer π-sulfur interactions. The information in this work is referable for the further development of selective inhibitors for specific isoforms of PI3K. 相似文献
965.
电化学DNA杂交检测技术因其快速、灵敏、低消耗和易于操作等优点而在临床医学、环境监测和药物分析等领域受到普遍关注。电化学DNA杂交指示剂是DNA电化学杂交传感器的重要组成部分,能与单链DNA和双链DNA通过不同的模式和作用力进行差异性结合。本文介绍了电化学杂交指示剂的定义及其在DNA电化学传感器中的重要性,根据分子结构上的特征差异,将非标记型电化学杂交指示剂分为有机染料(荧光素)、药物分子和金属配合物三类,并从中选取了各个类型中具有代表性的指示剂对它们的工作原理、研究进展和应用现状进行了比较和评述。对杂交指示剂的设计和开发前景,特别是满足基因芯片应用等方面做出了展望。 相似文献
966.
利用紫外-可见分光光度计在乙醇介质中研究了合成的4种对位取代四苯基钴卟啉对过亚硝酸根分解的催化作用. 首次发现钴卟啉可以催化ONOO-分解, 且对位带吸电子基团的钴卟啉比对位带供电子基团的钴卟啉催化活性高. TPPCoCl, T(p-CH3)PPCoCl, T(p-OCH3)PPCoCl和T(p-Cl)PPCoCl在乙醇中的kcat分别为1.69×102, 1.52×102, 1.43×102和1.20×103 mol-1•L•s-1. 动力学曲线和时间分辨谱证明这些钴卟啉是通过形成中间体催化过亚硝酸根分解的. 相似文献
967.
酰基硫脲衍生物的合成、结构表征及生物活性研究 总被引:2,自引:0,他引:2
在超声波辐射下, 以PEG-400为固-液相转移催化剂, 用芳胺与双酰基异硫氰酸酯反应, 合成出了15种新的结构不对称的双酰基硫脲类化合物(6和6')和9种新的分子中含酰胺基团的单酰基硫脲类化合物(7和7'). 利用元素分析, IR, 1H NMR, 13C NMR, APT, 1D NOE及2D NMR技术确定了所合成化合物6和6'及7和7'的结构, 并对它们NMR谱中低场C, H进行了归属. 杀菌、杀虫和除草活性筛选测定实验结果表明, 所测试化合物对瓜炭疽病菌均具有抑制作用, 其中6e抑制率最高, 达到62.4%; 目标化合物7a对黄瓜白粉病菌有一定的抑制作用. 单胺氧化酶活性测定实验表明:大部分目标化合物对单胺氧化酶具有一定的抑制活性, 其中浓度在1×10-3 mol•L-1时目标化合物6'c和6'd的抑制活性较强, 明显高于其它化合物. 目标化合物没有抗惊厥活性. 相似文献
968.
高度有序的二氧化钛纳米管阵列的制备及其光催化活性的研究 总被引:1,自引:0,他引:1
采用电化学阳极氧化法在钛表面构筑了一种结构有序、微米级的TiO2纳米管阵列膜层. 考察了制备电压、氧化时间、溶液搅拌等实验参数对TiO2纳米管阵列形貌和尺寸的影响. 应用SEM和XRD对膜层的形貌和晶型进行了分析和表征, 并通过TiO2纳米管阵列膜对甲基橙的光催化降解, 研究了TiO2纳米管阵列膜层结构与光催化活性的关系. 结果表明: 阳极电压和溶液搅拌对制备TiO2纳米管阵列的结构起到关键的作用. 控制20 V电压制备的TiO2纳米管阵列膜, 管长达2.6~3.3 μm, 经500 ℃热处理后具有最高的光催化活性, 其光催化性能明显优于一般的TiO2纳米颗粒膜. 相似文献
969.
A novel potassium complex KC9H9NO4SBr has been synthesized and characterized by IR spectra and single-crystal X-ray diffraction method. The crystal belongs to orthorhombic, space group Pbca with a = 0.74040(15), b = 0.74960(15), c = 4.2620(9) nm, V = 2.3654(8) nm^3, Mr = 346.24, Dc = 1.945 g/cm^3, Z = 8, F(000) = 1376, μ(MoKa) = 4.005mm^-1, GOOF = 1.021, R = 0.0471 and wR = 0.0872. In the crystal, the potassium ion is typically eight-coordinated, surrounded by eight O atoms from six (E)-2-(5-bromo-2-hydroxy-benzyli-deneamino)ethanesulfonate anions. The neighboring potassium ions are bridged by sulfonate groups into a two-dimensional layer structure, above and below which the 5-bromo-2-hydroxy-benzene rings are protruded. The activity against acetaminophen-induced hepatotoxicity of this complex was also studied, and found it can protect liver from hepatotoxicity induced by acetaminophen (AAP) to some extent. 相似文献
970.
The free radical copolymerization of (5-bromo-1-Benzofuran-2-yl)(phenyl)-O-methacrylketoxime (BPMKO) with 2-(4-acetylphenoxy)-2-oxoethyl-2-methylacrylate(AOEMA) has been carried out in 1, 4-dioxane at 65°C ± 1 and was analyzed by Fourier transform infrared, 1H-NMR, 13C-NMR and gel permeation chromatography. Elemental analysis was used to determine the molar fractions of BPMKO and AOEMA in the copolymers. The monomer–reactivity ratios were calculated according to the general copolymerization equation using Kelen-Tüdõs and Finemann-Ross linearization methods. The reactivity ratios indicated a tendency toward random copolymerization. The polydispersity indices of the polymers were determined by gel permeation chromatography and suggested a strong tendency for chain termination by disproportionation. The thermal behaviors of copolymers with various compositions were investigated by differential scanning calorimetry and thermogravimetric analysis. The glass-transition temperature of the copolymers increased with increasing BPMKO content in the copolymers. All the products showed moderate activity against different strains of bacteria and fungi. 相似文献