小分子抑制劑同時靶向癌癥代謝和表觀遺傳學(xué)：發(fā)現(xiàn)新型煙酰胺磷脂酰轉(zhuǎn)移酶（NAMPT）和組蛋白脫乙酰酶（HDAC）雙抑制劑譯者：啊達(dá) 癌癥代謝和表觀遺傳學(xué)是抗癌藥物研究領(lǐng)域中最深入的研究領(lǐng)域之一。同時在這里,我們報告了同時抑制煙酰胺磷酸核糖轉(zhuǎn)移酶（NAMPT）和組蛋白脫乙酰酶（HDAC）的第一個小分子,分別是癌癥新陳代謝和表觀遺傳學(xué)的兩個重要靶點。通過基于迭代結(jié)構(gòu)的藥物設(shè)計、化學(xué)合成和生物分析，成功地確定了一個高效的雙NAMPT和HDAC抑制劑?；衔?5對NAMPT(IC50 = 31 nM)和HDAC1(IC50 = 55 nM)均有良好的平衡活性。它能有效誘導(dǎo)細(xì)胞凋亡和自噬，最終導(dǎo)致細(xì)胞死亡。重要的是，化合物35在HCT116異種移植模型中顯示了良好的抗腫瘤療效。這一概念驗證研究證明了發(fā)現(xiàn)一種靶向癌癥代謝和表觀遺傳學(xué)抑制劑的可行性，并為多靶點抗腫瘤藥物的發(fā)現(xiàn)提供了一種有效的策略。 Small Molecule Inhibitors Simultaneously Targeting Cancer Metabolism and Epigenetics: Discovery of Novel Nicotinamide Phosphoribosyltransferase (NAMPT) and Histone Deacetylase (HDAC) Dual Inhibitors J. Med. Chem. September 8, 2017 Cancer metabolism and epigenetics are among the most intensely pursued research areas in anticancer drug discovery. Here we report the first small molecules that simultaneously inhibit nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC), two important targets of cancer metabolism and epigenetics, respectively. Through iterative structure-based drug design, chemical synthesis and biological assays, a highly potent dual NAMPT and HDAC inhibitor was successfully identified. Compound 35 possessed excellent and balanced activities against both NAMPT (IC50 = 31 nM) and HDAC1 (IC50 = 55 nM). It could effectively induce cell apoptosis and autophagy and ultimately led to cell death. Importantly, compound 35 showed excellent in vivo antitumor efficacy in the HCT116 xenograft model. This proof-of-concept study demonstrates the feasibility of discovering an inhibitor targeting cancer metabolism and epigenetics and provides an efficient strategy for multi-target antitumor drug discovery. http://pubs./doi/10.1021/acs.jmedchem.7b00467 白光誘導(dǎo)使用吩嗪染料的石墨烯共價修飾 譯者：小七 在此，我們報道了一種新穎的方法，用光活性染料對石墨烯納米孔進(jìn)行共價改性。采用白光法對石墨烯表面進(jìn)行光化學(xué)生成吩嗪基，并通過分光光度法對反應(yīng)進(jìn)行光譜分析。對改性材料的描述是由FTIR、XRD、UV-vis吸收、熒光、拉曼光譜和SEM成像技術(shù)進(jìn)行的。這種混合材料的溶解度提高了，顯示了一種光帶隙，在可見光波段有很高的發(fā)射距離。 White light induced covalent modification of graphene using phenazine dye Chem. Commun. Herein, we report a novel strategy for a covalent modification of graphene nanoplatelets with photoactive dyes. Functionalization of the graphene surface was carried out using white light to photochemically generate phenazine radicals and the reaction progress was followed up spectrophotometrically. Characterization of the modified material was carried out by FTIR, XRD, UV-vis absorption, fluorescence, Raman spectroscopy and SEM imaging. This hybrid material has improved solubility, shows an optical band gap of 1.95 eV and is highly emissive in the visible wavelength region. http://pubs./en/content/articlelanding/2017/cc/c7cc05158a#!divAbstract 通過分子內(nèi)銠催化將氰基噻二唑轉(zhuǎn)化成雙環(huán)異噻唑譯者：阿雷 一種分子內(nèi)的銠催化轉(zhuǎn)化：含有酯，酰胺，或醚作為連接劑的可獲得的氰基硫二唑。它提供了廣泛的雙環(huán)異噻唑，與分子氮的釋放結(jié)合在一起，很好地達(dá)到了極好的產(chǎn)量。結(jié)果表明，硫酰亞基碳原子中的碳原子具有親核性，硫原子具有親電性。 Synthesis of Bicyclic Isothiazoles through an Intramolecular Rhodium-Catalyzed Transannulation of Cyanothiadiazoles J. Org. Chem. Publication Date (Web): September 9, 2017 An intramolecular rhodium-catalyzed transannulation of readily available cyanothiadiazoles containing an ester, amide, or ether as a linker is described. It provides a wide range of bicyclic isothiazoles in good to excellent yields together with the release of molecular nitrogen. These results indicate that the carbon atom in the α-thiavinyl carbene is nucleophilic and that the sulfur atom is electrophilic. http://pubs./doi/10.1021/acs.joc.7b02077 通過前體純化減少混合鈣鈦礦膜的內(nèi)在缺譯者：啊達(dá) 一種簡單的化學(xué)過程是以可伸縮的方式發(fā)展的，從一開始就減少了鈣鈦礦吸收劑的陷阱狀態(tài)。結(jié)果表明，碘銨離子濃度明顯降低，合成膜中陷阱密度降低，導(dǎo)致鈣鈦礦太陽能電池的功率轉(zhuǎn)換效率從16.5%提高到18.5%。 Reduction of Intrinsic Defects in Hybrid Perovskite Films via Precursor PurificationChem. Commun. A simple chemical process was developed in a scalable manner, to reduce trap states in perovskite absorbers from the very beginning. Obvious decrease of I2 in methylammonium iodide and the decrease of trap density in the resultant films were identified, which leads to the power conversion efficiencie (PCE) of perovskite solar cells (PSCs) increases from 16.5% to 18.5%. http://pubs./en/content/articlelanding/2017/cc/c7cc05590k#!divAbstract 超分子順鉑 - 伏立諾他納米藥物克服癌癥協(xié)同治療中的耐藥性 譯者：啊達(dá) Supramolecular cisplatin-vorinostat nanodrug for overcoming drug resistance in cancer synergistic therapy J. Control. Release Cisplatin is a widely used anticancer drug in clinic. However, it may induce drug resistance after a course of treatment and it is difficult to accumulate at tumor site selectively, which result in clinic failure and side effects. We successfully bound cisplatin with vorinostat (a FDA-approved histone deacetylase inhibitor) to form a supramolecular conjugate, which can further self-assemble into nanoparticles. The nanodrug can retain in blood stream for a long time, accumulate in tumor site and hydrolyze to release the two drugs for synergistic therapy. In vivo experiments highlighted the great advantage of the supramolecular nanodrug, because it ensured the two drugs reaching cancer tissue simutaneously. Free cisplatin or cisplatin/vorinostat mixture had negligible or limited effects on A549/DR tumor growth. On the contrary, the tumor inhibitory rate approached 99% with little systemic toxicity if the dose of cisplatin-vorinostat nanodrug reached 10 mg/kg body weight, thus suggesting this supramolecular nanodrug as a promising treatment of drug resistance cancer. http://www./science/article/pii/S0168365917308301 如果你熱愛化學(xué)，想了解第一手學(xué)術(shù)資訊，英語很溜，還有一些空閑，想做個兼職，賺點外快……加入ChemBeanGo，成為我們的智囊團(tuán)！ (詳情:http://www./news/art?id=3057) 了解更多最全、最新論文快訊 登錄CBG官網(wǎng)（www.） 下載ChemBeanGo APP CBG資訊 ∣知識就是力量 |
|
|
