检索结果-南通市图书馆

Lethaclado acid A and B from Lethariella cladonioides

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2007年第12期18卷 1515-1517页

作者： Xin Huang Jun Li Jian Hua Shen Jun Hua Chen drug discovery and Design Centre State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 201203 PR China

Two new compounds, lethaclado acid A （1） and B （2）, were isolated from the acetone extract ofLethariella cladonioides. Their structures were elucidated on the basis of 1D and 2D NMR as well as ESI-MS spectral data.

关键词： Lethariella cladonioides Depside Depsidone Lethaclado acid A Lethaclado acid B

Novel cyclophilin D inhibitors derived from quinoxaline exhibit highly inhibitory activity against rat mitochondrial swelling and Ca2+ uptake/release

在线全文

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2005年第10期26卷 1201-1211页

作者： Hong-xia GUO~(2,3), Feng WANG~(2,3), Kun-qian YU~3, Jing CHEN~3, Dong-lu BAI~3, Kai-xian CHEN~3, Xu SHEN~(3,4,5), Hua-liang JIANG~(3,4,5) ~3 drug discovery and Design Center, State Key Laboratory of drug Research, Shanghai Institute of Materia Medica, Shanghai institutes for Biologieal Sciences Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China ~4 School of Pharmacy, East China University of Science and Technology Shanghai 200237, China drug discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Shanghai 201203 China.

Aim: To investigate methods for identifying specific cyclophilin D （CypD） inhibitors derived from quinoxaline, thus developing possible lead compounds toinhibit mitochondrial permeability transition （MPT） pore opening. Methods: Kinetic analysis of the CypD/inhibitor interaction was quantitatively performed byusing surface plasmon resonance （SPR） and fluorescence titration （FT） ***50values of these inhibitors were determined by PPIase inhibition activity ***: All the equilibrium dissociation constants （KD） of the seven compoundsbinding to CypD were below 10 μmol/L. The IC50values were all consistent withthe SPR and FT results. Compounds GW2, 5, 6, and 7 had high inhibition activitiesagainst Ca2+-dependent rat liver mitochondrial swelling and Ca2+uptake/*** GW5 had binding selectivity for CypD over CypA. Conclusion: Theagreement between the measured IC50values and the results of SPR and FT suggests that these methods are appropriate and powerful methods for fyingCypD inhibitors. The compounds we screened using these methods （GW1-7） arereasonable CypD inhibitors. Its potent ability to inhibit mitochondrial swelling and the binding selectivity of GW5 indicates that GW5 could potentially be used for inhibiting MPT pore opening.

关键词： cyclophilin quinoxalines surface plasmon resonance mitochondrial permeability transition: fluorescence titration inhibitor

Modulation of long-term potentiation in the hippocampus by pharmacological approach:A novel strategy for the development of cognitive enhancers

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Chinese Science Bulletin 2010年第30期55卷 3374-3382页

作者： YANG YuanJian WU PengFei WANG Fang CHEN Jian Guo Department of Pharmacology Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Key Laboratory of Neurological Diseases (HUST) Ministry of Education of China Wuhan 430030 China institutes of biomedicine and drug discovery Huazhong University of Science and Technology Wuhan 430030 China

Learning and memory not only provide the foundations of cognition, but are also closely related to sensory and motor function. Neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease are accompanied by deficits in synaptic function and cognition to varying degrees. The discovery of long-term potentiation (LTP) of hippocampal synaptic transmission, which has been recognized as a classical model of learning and memory at the cellular level, has spurred substantial progress in the development of cognitive enhancers in the past 20 years. Following intensive investigations into LTP, a variety of compounds and biologically active substances have been found to modulate hippocampal LTP via numerous molecular mechanisms including regulating presynaptic neurotransmitter release, postsynaptic N-methyl D-aspartate (NMDA) receptor activity, postsynaptic signal transduction and gene transcription. This review focuses on the progress of investigations into the overarching mechanisms of LTP, the drugs modulating LTP and prospects for the development of new drugs for treating cognitive impairments in the future.

关键词：药物治疗海马生物活性物质阿尔茨海默氏病突触传递电位调制分子机制

New Ligands for Copper-Catalyzed C-N Coupling Reactions at Gentle Temperature

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Chemistry 2014年第8期32卷 685-688页

作者： Jinyue Su Yatao Qiu Sheng Jiang Dayong Zhang Center of drug discovery China Pharmaceutical UniversityNanjingJiangsu 210009China Laboratory of Medicinal Chemistry Guangzhou Institute of Biomedicine and HealthGuangzhouGuangdong 510530China

Pyridin-2-ol-N-oxide was designed as an efficient ligand for the coupling reaction of aryl iodides,aryl bromides and aryl chlorides,respectively,with primary amines,cyclic secondary amines or N-containing heterocycles at room or moderate *** catalytic system showed great functional groups tolerance and excellent selective reactivity.

关键词： C-N coupling reactions copper corss-coupling pyridin-2-ol-N-oxide Ullmann reaction

Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2006年第1期27卷 100-110页

作者： Gui-xia LIU~(2,3,4) Jin-zhi TAN~2 Chun-ying NIU~2 Jian-hua SHEN~(2,3) Xiao-min LUO~2 Xu SHEN~(2,3) Kai-xian CHEN~2 Hua-liang JIANG~(2,3,4)2 Center for drug discovery and Design,State Key Laboratory of drug Research,Shanghai Institute of Materia Medica,Shanghai institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 201203,China 3 School of Pharmacy,East China University of Science and Technology Shanghai 200237,China Center for drug discovery and Design State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China School of Pharmacy East China University of Science and Technology Shanghai China

Aim:To investigate the dynamic properties of protein-tyrosine phosphatase (PTP)1B and reveal the structural factors responsible for the high inhibitory potencyand selectivity of the inhibitor SNA for ***:We performed moleculardynamics (MD) simulations using a long time-scale for both PTP1B and PTP1Bcomplexed with the inhibitor SNA,the most potent and selective PTP1B inhibitorreported to *** trajectories were analyzed by using principal ***:Trajectory analyses showed that upon binding the ligand,theflexibility of the entire PTP1B molecule *** most notable change is themovement of the *** simulation results also indicated that electro-static interactions contribute more to PTP 1B-SNA complex conformation than thevan der Waals interactions,and that Lys41,Arg47,and Asp48 play important rolesin determining the conformation of the inhibitor SNA and in the potency andselectivity of the *** these,Arg47 contributed *** results werein agreement with previous experimental ***:The informationpresented here suggests that potent and selective PTP1B inhibitors can be de-signed by targeting the surface residues,for example the region containing Lys41,Arg47,and Asp48,instead of the second phosphate binding site (besides theactive phosphate binding site).

关键词： molecular dynamics simulation principal component analysis protein-tyrosine phosphatase 1B type 2 diabetes

Mapping the Binding Site of P53 on UBC9 by NMR Spectroscopy

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of Chemistry 2002年第10期20卷 937-943页

作者：林东海 Department of Biochemistry The Hong Kong University of Science & Technology Hong Kong China Center for drug discovery and Design State Key Laboratory of Drug Research Shanghai Institute of Meteria Medica Shanghai Institutes of Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

Human UBC9 is a member of the E2 family of proteins. However, instead of conjugating to ubiquitin, it conjugates to a ubiquitin homologue SUMO-1 (also known as UBL1, GMP1, SMTP3, PICT-1 and sentrin). The SUMO-1 conjugation pathway is very similar to that of ubiquitin with regard to the primary sequences of the ubiquitin activating enzymes (E1), the three-dimensional structures of the ubiquitin conjugating enzymes (E2), and the chemistry of the overall conjugation pathway. The interaction of p53 and UBC9, the E2 of the SUMO-1 pathway, has been studied by nuclear magnetic resonance spectroscopy. A peptide corresponding to the nuclear localization domain of p53 specifically interacts with UBC9 and this interaction is likely to be important for conjugation of p53 with SUMO-1. The largest chemical shift changes on UBC9 occur at residues 94 and 129-135. This region is adjacent to the active site and has significant dynamic behavior on the μs-ms and ps-ns timescales. Correlation of chemical shift changes and mobility of these residues further suggest the importance of these residues in substrate recognition.

关键词： NMR protein-peptide interaction SUMO-1 pathway E2 enzyme p53

A practical synthesis of trifluorophenyl R-amino acid:The key precursor for the new anti-diabetic drug sitagliptin

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2009年第12期20卷 1397-1399页

作者： Li Li Zeng Ying Jie Ding Gui Cheng Zhang Hong Rui Song Wen Hui Hu Laboratory of Anti-diabetic drug discovery Center for Synthetic and Natural Drugs Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510663 China The School of Pharmaceutical Engineering Shenyang Pharmaceutical University Shenyang 110016 China

Sitagliptin is the first new anti-diabetic drug in DPP-Ⅳ inhibitor class. The general synthesis of sitagliptin is by coupling of the β-amino acid fragment with the heterocycle fragment. Though the specific β-amino acid can be easily made from the corresponding R-amino acid by Arndt-Eistert hornologation, the optically pure precursor R-amino acid is difficult to prepare. We herein reported a practical protocol to make the trifluorophenyl substituted R-amino acid 4 in 〉99.9% ee and 40.3% yield by the enzymatic resolution employing enantioselective hydrolysis and a general separation procedure. This protocol requires only cheap starting materials and friendly reaction condition. The procedure not only allows people to prepare the drug substance, but also provides an alternative method for prepareing the rare α-amino acid and the subsequent β-amino acid.

关键词： Sitagliptin β-Amino acid DPP-Ⅳ inhibitor Practical synthesis

Evaluation of Benzamide Derivatives as New Influenza A Nucleoprotein Inhibitors

在线全文

学校读者我要写书评

暂无评论

Open Journal of Medicinal Chemistry 2016年第3期6卷 43-50页

作者： Jinxi Liao Huimin Cheng Junting Wan Panyu Chen Yingjun Li Ke Ding Micky D. Tortorella Zhengchao Tu Yanmei Zhang drug discovery Pipeline Guangzhou Institutes of Biomedicine and Health Science City Guangzhou China Institute of Chemical Biology Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China University of Chinese Academy of Sciences Beijing China

Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC50 values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.

关键词： Benzamides Nucleoprotein Anti-Influenza NP Inhibitors Nucleozin

A Therapeutic Sheep in Metastatic Wolf’s Clothing: Trojan Horse Approach for Cancer Brain Metastases Treatment

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Nano-Micro Letters 2022年第7期14卷 140-156页

作者： Hai-jun Liu Mingming Wang Shanshan Shi Xiangxiang Hu Peisheng Xu Department of drug discovery and Biomedical Sciences College of PharmacyUniversity of South CarolinaColumbiaSC 29208USA

Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a Trojan horse strategy-based nanocarrier has been developed by integrating the cell membrane of a brain-homing cancer cell and a polymeric drug depot. With the camouflage of a MDA-MB-231/Br cell membrane, doxorubicin-loaded poly(D, L-lactic-co-glycolic acid) nanoparticle(DOX-PLGA@CM) shows enhanced cellular uptake and boosted killing potency for MDA-MB-231/Br cells. Furthermore, DOX-PLGA@CM is equipped with naturally selected molecules for BBB penetration, as evidenced by its boosted capacity in entering the brain of both healthy and early-stage BMBC mouse models. Consequently, DOX-PLGA@CM effectively reaches the metastatic tumor lesions in the brain, slows down cancer progression, reduces tumor burden, and extends the survival time for the BMBC ***, the simplicity and easy scale-up of the design opens a new window for the treatment of BMBC and other brain metastatic cancers.

关键词： Trojan horse Brain metastasis Blood-brain barrier Cell membrane Nanomedicine