共查询到20条相似文献,搜索用时 15 毫秒
1.
Sean P. Murphy Rona J. Lee Megan E. McClean Heather E. Pemberton Takuma Uo Richard S. Morrison Chinthasagar Bastian Selva Baltan 《Journal of neurochemistry》2014,129(3):509-515
The administration of pan histone deacetylase (HDAC) inhibitors reduces ischemic damage to the CNS, both in vitro and in animal models of stroke, via mechanisms which we are beginning to understand. The acetylation of p53 is regulated by Class I HDACs and, because p53 appears to play a role in ischemic pathology, the purpose of this study was to discover, using an in vitro white matter ischemia model and an in vivo cerebral ischemia model, if neuroprotection mediated by HDAC inhibition depended on p53 expression. Optic nerves were excised from wild‐type and p53‐deficient mice, and then subjected to oxygen–glucose deprivation in the presence and absence of a specific inhibitor of Class I HDACs (MS‐275, entinostat) while compound action potentials were recorded. Furthermore, transient focal ischemia was imposed on wild‐type and p53‐deficient mice, which were subsequently treated with MS‐275. Interestingly, and in both scenarios, the beneficial effects of MS‐275 were most pronounced when p53 was absent. These results suggest that modulation of p53 activity is not responsible for MS‐275‐mediated neuroprotection, and further illustrate how HDAC inhibitors variably influence p53 and associated apoptotic pathways.
2.
3.
Design,synthesis, and characterization of α, β‐unsaturated carboxylic acid,and its urea based derivatives that explores novel epigenetic modulators in human non‐small cell lung cancer A549 cell line 下载免费PDF全文
Anusha Chidambaram Kavya Sundararaju Ramesh K. Chidambaram Rajasekaran Subbiah John M. Jayaraj Karthikeyan Muthusamy Ravikumar Vilwanathan 《Journal of cellular physiology》2018,233(7):5293-5309
4.
5.
Novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes: Synthesis,characterization, acetylcholinesterase,butyrylcholinesterase, and carbonic anhydrase inhibitory properties 下载免费PDF全文
Parham Taslimi Sabiya Osmanova Cuneyt Caglayan Fikret Turkan Sabira Sardarova Vagif Farzaliyev Afsun Sujayev Nastaran Sadeghian İlhami Gulçin 《Journal of biochemical and molecular toxicology》2018,32(9)
The thiolation reaction was carried out in a benzene solution at 80°C and p‐substituted ketones and mercaptoacetic acid in a molar ratio (1:4) of in the presence of a catalytic amount of toluene sulfonic acids. The enzyme inhibition activities of the novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives were investigated. These novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives showed good inhibitory action against acetylcholinesterase (AChE) butyrylcholinesterase (BChE), and human carbonic anhydrase I and II isoforms (hCA I and II). AChE inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. Many clinically established drugs are carbonic anhydrase inhibitors, and it is highly anticipated that many more will eventually find their way into the market. The novel synthesized compounds inhibited AChE and BChE with Ki values in the range of 0.64–1.47 nM and 9.11–48.12 nM, respectively. On the other hand, hCA I and II were effectively inhibited by these compounds, with Ki values between 63.27–132.34 and of 29.63–127.31 nM, respectively. 相似文献
6.
7.
Doan Thanh Hieu Duong Tien Anh Pham‐The Hai Nguyen Thi Thuan Le‐Thi‐Thu Huong Eun Jae Park A. YoungJi Jong SoonKang Phan Thi PhuongDung Sang‐Bae Han Nguyen‐Hai Nam 《化学与生物多样性》2019,16(4)
The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5b ) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5c ) (IC50 values, 0.10–0.16 μm ) were found to be approximately 30‐fold more cytotoxic than SAHA (IC50 values of 3.29–3.67 μm ). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5a ; IC50 values of 0.21–0.38 μm ) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC50 values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c , strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA. 相似文献
8.
该文主要为了研究斗米虫蛋白的体外抗肿瘤活性及其免疫调节作用。提取斗米虫总蛋白,逐级盐析分为3个部分,透析除盐后得到不同蛋白部位,并采用SDS-PAGE检测斗米虫不同蛋白部位的分子量;利用MTT法、流式细胞术等方法研究斗米虫蛋白对人胃癌细胞MFC和小鼠乳腺癌细胞4T1增殖、迁移和凋亡的作用。MTT法研究斗米虫蛋白对小鼠单核巨噬细胞RAW264.7和人脐静脉内皮细胞HUEVC增殖的影响;荧光微球吞噬实验检测斗米虫蛋白对RAW264.7细胞吞噬能力的影响;Griess法检测对RAW264.7细胞释放NO能力的影响;ELISA法检测对RAW264.7细胞的IL-6、TNF-α和IL-1β分泌量;RT-PCR法检测不同浓度的斗米虫蛋白作用后RAW264.7细胞中TNF-α、IL-1、TLR4、MIR-7、IFN-γ、TRL-4、IL-6以及4T1细胞中MMP2、MMP9、STAT3、c-Myc和Sdf1 mRNA水平变化。结果显示,斗米虫蛋白主要分子量集中于63 kDa,斗米虫蛋白对人胃癌细胞MFC及小鼠乳腺癌细胞4T1的增殖表现出较好抑制作用,并呈现出一定剂量依赖关系(P<0.05),对HUEVC细胞没有细胞毒性,对RAW264.7细胞表现出较好的促进增殖的作用(P<0.05)。斗米虫蛋白实验组与正常组细胞相比可以抑制4T1细胞的迁移(P<0.01),可诱导MFC和4T1细胞凋亡(P<0.05);斗米虫蛋白能够提高RAW264.7细胞的吞噬活性、NO释放量、TNF-α、1L-1β和IL-6分泌量及TNF-α、IL-1、TLR4、MIR-7、IFN-γ和IL-6细胞因子的mRNA水平以及能显著下调4T1细胞中MMP2、MMP9、STAT3、c-Myc和Sdf1 mRNA水平(P<0.05,P<0.01)。由此推论,斗米虫蛋白具有较好的体外抗肿瘤活性并且具有潜在的免疫调节作用。 相似文献
9.
10.
11.
12.
7‐Methoxy‐(9H‐β‐Carbolin‐1‐il)‐(E)‐1‐Propenoic Acid,a β‐Carboline Alkaloid From Eurycoma longifolia,Exhibits Anti‐Inflammatory Effects by Activating the Nrf2/Heme Oxygenase‐1 Pathway 下载免费PDF全文
Nguyen Hai Dang Young‐Yeon Choo Nguyen Tien Dat Nguyen Hoai Nam Chau Van Minh Jeong‐Hyung Lee 《Journal of cellular biochemistry》2016,117(3):659-670
13.
14.
Purification of glutathione S‐transferase enzyme from quail liver tissue and inhibition effects of (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(aryl)acryloyl)phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione derivatives on the enzyme activity 下载免费PDF全文
Yusuf Temel Umit M. Koçyigit M. Şerif Taysı Faik Gökalp Meliha Burcu Gürdere Yakup Budak Mustafa Ceylan İlhami Gülçin Mehmet Çiftci 《Journal of biochemical and molecular toxicology》2018,32(3)
The use of quail meat and eggs has made this animal important in recent years, with its low cost and high yields. Glutathione S‐transferases (GST, E.C.2.5.1.18) are an important enzyme family, which play a critical role in detoxification system. In our study, GST was purified from quail liver tissue with 47.88‐fold purification and 12.33% recovery by glutathione agarose affinity chromatography. The purity of enzyme was checked by SDS‐PAGE method and showed a single band. In addition, inhibition effects of (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(aryl)acryloyl)phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7methanoisoindole‐1,3(2H)‐dion derivatives ( 1a–g ) were investigated on the enzyme activity. The inhibition parameters (IC50 and Ki values) were calculated for these compounds. IC50 values of these derivatives ( 1a–e ) were found as 23.00, 15.75, 115.50, 10.00, and 28.75 μM, respectively. Ki values of these derivatives ( 1a–e ) were calculated in the range of 3.04 ± 0.50 to 131.50 ± 32.50 μM. However, for f and g compounds, the inhibition effects on the enzyme were not found. 相似文献
15.
Quantitative phosphoproteomic analysis reveals γ‐bisabolene inducing p53‐mediated apoptosis of human oral squamous cell carcinoma via HDAC2 inhibition and ERK1/2 activation 下载免费PDF全文
Yu‐Jen Jou Chao‐Jung Chen Yu‐Ching Liu Tzong‐Der Way Chih‐Ho Lai Chun‐Hung Hua Ching‐Ying Wang Su‐Hua Huang Jung‐Yie Kao Cheng‐Wen Lin 《Proteomics》2015,15(19):3296-3309
γ‐Bisabolene, one of main components in cardamom, showed potent in vitro and in vivo anti‐proliferative activities against human oral squamous cell carcinoma (OSCC). γ‐Bisabolene activated caspases‐3/9 and decreased mitochondrial memebrane potential, leading to apoptosis of OSCC cell lines (Ca9‐22 and SAS), but not normal oral fibroblast cells. Phosphoproteome profiling of OSCC cells treated with γ‐bisabolene was identified using TiO2‐PDMS plate and LC‐MS/MS, then confirmed using Western blotting and real‐time RT‐PCR assays. Phosphoproteome profiling revealed that γ‐bisabolene increased the phosphorylation of ERK1/2, protein phosphatases 1 (PP1), and p53, as well as decreased the phosphorylation of histone deacetylase 2 (HDAC2) in the process of apoptosis induction. Protein–protein interaction network analysis proposed the involvement of PP1‐HDAC2‐p53 and ERK1/2‐p53 pathways in γ‐bisabolene‐induced apoptosis. Subsequent assays indicated γ‐bisabolene eliciting p53 acetylation that enhanced the expression of p53‐regulated apoptotic genes. PP1 inhibitor‐2 restored the status of HDAC2 phosphorylation, reducing p53 acetylation and PUMA mRNA expression in γ‐bisabolene‐treated Ca9‐22 and SAS cells. Meanwhile, MEK and ERK inhibitors significantly decreased γ‐bisabolene‐induced PUMA expression in both cancer cell lines. Notably, the results ascertained the involvement of PP1‐HDAC2‐p53 and ERK1/2‐p53 pathways in mitochondria‐mediated apoptosis of γ‐bisabolene‐treated cells. This study demonstrated γ‐bisabolene displaying potent anti‐proliferative and apoptosis‐inducing activities against OSCC in vitro and in vivo, elucidating molecular mechanisms of γ‐bisabolene‐induced apoptosis. The novel insight could be useful for developing anti‐cancer drugs. 相似文献
16.
17.
Daniela Cecconi Massimo Donadelli Elisa Dalla Pozza Sara Rinalducci Lello Zolla Maria Teresa Scupoli Pier Giorgio Righetti Aldo Scarpa Marta Palmieri Dr. 《Proteomics》2009,9(7):1952-1966
Our research group recently reported that pancreatic endocrine cancer cell lines are sensitive to the HDAC inhibitor trichostatin A (TSA). In the present paper, we show that the combined treatment of pancreatic endocrine tumour cell lines with TSA and the DNA methyltransferase inhibitor 5‐aza‐2′‐deoxycytidine (DAC) determines a strong synergistic inhibition of proliferation mainly due to apoptotic cell death. Proteomic analysis demonstrates that the modulation of specific proteins correlates with the antiproliferative effect of the drugs. A schematic network clarifies the most important targets or pathways involved in pancreatic endocrine cancer growth inhibition by single or combined drug treatments, which include proteasome, mitochondrial apoptotic pathway and caspase related proteins, p53 and Ras related proteins. A comparison between the patterns of proteins regulated by TSA or DAC in endocrine and ductal pancreatic cancer cell lines is also presented. 相似文献
18.
Quinazoline‐Based Hydroxamic Acids: Design,Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity 下载免费PDF全文
Doan Thanh Hieu Duong Tien Anh Pham‐The Hai Le‐Thi‐Thu Huong Eun Jae Park Jeong Eun Choi Jong Soon Kang Phan Thi Phuong Dung Sang‐Bae Han Nguyen‐Hai Nam 《化学与生物多样性》2018,15(6)
In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N‐hydroxybenzamides incorporating quinazoline heterocycles ( 4a – 4i , 6a – 6i ). Bioevaluation showed that these quinazoline‐based hydroxamic acids and N‐hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI‐H23, lung). In term of cytotoxicity, several compounds, e.g., 4g , 4c , 4g – 4i , 6c , and 6h , displayed from 5‐ up to 10‐fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub‐micromolar range. Some compounds, e.g., 4g , 6c , 6e , and 6h , were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g , 6c , and 6g , while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates. 相似文献
19.
Combinatorial Synthesis of New Pyrimidine‐ and Purine‐β‐d‐Ribonucleoside Nucleolipids: Their Distribution Between Aqueous and Organic Phases and Their In Vitro Activity Against Human‐ and Rat Glioblastoma Cells In Vitro 下载免费PDF全文
Katharina Hammerbacher Katharina Görtemaker Christine Knies Eugenia Bender Gabriel A. Bonaterra Helmut Rosemeyer Ralf Kinscherf 《化学与生物多样性》2018,15(9)
20.
In Vitro and In Vivo Evaluation of N‐{2‐[4‐(3‐Cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐[11C]methoxybenzamide,a Positron Emission Tomography (PET) Radioligand for Dopamine D4 Receptors,in Rodents 下载免费PDF全文
Marcello Leopoldo Svetlana V. Selivanova Adrienne Müller Enza Lacivita Simon M. Ametamey 《化学与生物多样性》2014,11(9):1298-1308
The D4 dopamine receptor belongs to the D2‐like family of dopamine receptors, and its exact regional distribution in the central nervous system is still a matter of considerable debate. The availability of a selective radioligand for the D4 receptor with suitable properties for positron emission tomography (PET) would help resolve issues of D4 receptor localization in the brain, and the presumed diurnal change of expressed protein in the eye and pineal gland. We report here on in vitro and in vivo characteristics of the high‐affinity D4 receptor‐selective ligand N‐{2‐[4‐(3‐cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐[11C]methoxybenzamide ([11C] 2 ) in rat. The results provide new insights on the in vitro properties that a brain PET dopamine D4 radioligand should possess in order to have improved in vivo utility in rodents. 相似文献