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Chinese Chemical Letters 2020年第7期31卷 1881-1886页

作者： Jianbing Wu Wei Yin Yinqiu Zhang Hui Ye Yunman Li Jide Tian Zhangjian Huang Yihua Zhang State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Drug DiscoveryChina Pharmaceutical UniversityNanjing 210009China State Key Laboratory of Natural Medicines Department of PhysiologyChina Pharmaceutical UniversityNanjing 210009China department of Molecular and Medical Pharmacology University of CaliforniaLos AngelesCA 90095United States

To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide(NBP),we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids(S1-S8).These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,S2 was 30-fold more water-soluble,and over 10-fold more potent in inhibition of platelet aggregation,as well as reduced ROS generation and protected primary neuronal cells from OGD/Rinduced damage,in comparison with NB ***,S2 was more active than its three moieties alone or in combination,suggesting that the activity of S2 may be attributed to the synergistic effects of these ***,in vivo studies indicated that S2 not only possessed good pharmacokinetic profile,but also improved NBP distribution in rodent brain,suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1(GLUT1)on blood-brain barrier(BBB),promoting it to penetrate through *** findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke,warranting further study.

关键词： 3-n-Butylphthalide Ferulic acid Glucose Hybrids Ischemic Brain-blood barrier

Glioblastoma multiforme:Diagnosis, treatment, and invasion

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The Journal of Biomedical Research 2023年第1期37卷 47-58页

作者： Jiawei Li Lili Feng Yingmei Lu department of Physiology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China The First Clinical Medical College of Nanjing Medical University NanjingJiangsu 211166China Key Laboratory of Cardiovascular&Cerebrovascular Medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China

Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized therapeutic options. However, due to the intrinsic invasion and metastasis features and the resistance to chemotherapy, the survival rate of glioblastoma patients remains unsatisfactory. To improve the current situation, much more research is needed to provide comprehensive knowledge of GBM. In this review, we summarize the latest updates on GBM treatment and invasion. Firstly, we review the traditional and emerging therapies that have been used for GBM treatment. Given the limited efficiency of these therapies, we further discuss the role of invasion in GBM recurrence and progression, and present current research progress on the mode and mechanisms of GBM invasion.

关键词： glioblastoma multiforme diagnosis treatment patterns of invasion invasion mechanism

Synthesis of the key intermediate of ramelteon

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Chinese Chemical Letters 2011年第3期22卷 264-267页

作者： Shan Bao Yu Hao Min Liu Yu Luo Wei Lub department of Chemistry East China Normal University Shanghai 200062 China Institute of drug discovery and Development East China Normal University Shanghai 200062 China

Asymmetric conjugated addition of allylcopper reagents derived from an allyl Grignard reagent and CuBr·Me_2S to chiralα,β-unsaturated N-acyl oxazolidinones has been *** synthetic procedure was applied to the prepar... 详细信息

关键词： Ramelteon Asymmetric Michael addition Synthesis

A practical synthesis of 2-amino-5-methoxylpropiophenone

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Chinese Chemical Letters 2011年第1期22卷 1-4页

作者： Shan Bao Yu Li Juan Zhang Yu Luo Wei Lu department of Chemistry East China Normal University Shanghai 200062 China Institute of drug discovery and Development East China Normal University Shanghai 200062 China

This paper described a practical five-step synthetic approach for 2-amino-5-methoxylpropiophenone in 45% overall yield, using 3-chloropropiopbenone as the starting material. The advantages of this procedure include sh... 详细信息

关键词： Camptothecin SN38 Synthesis

A new synthetic approach to phosphatidylethanolamine

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Chinese Chemical Letters 2012年第2期23卷 154-156页

作者： Yang Song Wei Yuan Yu Luo Wei Lu department of Chemistry East China Normal UniversityShanghai 200062China Institute of drug discovery and Development East China Normal UniversityShanghai 200062China

A new synthetic method for phosphatidylethanolamine head group was developed via ring-opening of cyclic dioxaphospholane 2 with sodium azide and subsequent *** advantage of this strategy included short reaction steps,... 详细信息

关键词： Phosphatidylethanolamine Synthesis

APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells

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Science China(Life Sciences) 2017年第6期60卷 617-626页

作者： Shuran Li Xueyang Bao Duowei Wang Linjun You Xianjing Li Hongbao Yang Jinsong Bian Yun Wang Yong Yang State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease Center for New Drug Safety Evaluation and Research China Pharmaceutical University department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore

APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma(HCC) and APOBEC3B(A3B) remains unknown. It has been confirmed that interleukin-6(IL-6)has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3 B in HepG2 cells. A3 B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3 B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3 B and IL-6, and thereby promoted the prolonged non-resolving inflammation. Collectively, these findings suggest that A3 B is essential for oncogenesis of HCC, and is a potential target for preventive intervention.

关键词： APOBEC3B interleukin-6 hepatitis hepatocellular carcinoma HuR

Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture

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Neural Regeneration Research 2014年第24期9卷 2128-2131页

作者： Akira Oda Hidekazu Tanaka CNS drug discovery Unit Pharmaceutical Research Division Takeda Pharmaceutical Company Limited Laboratory of Pharmacology Department of Biomedical Sciences College of Life Sciences Ritsumeikan University

The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.

关键词： cholinergic system nicotinic acetylcholine receptors (nAChRs) Alzheimer's disease (AD) synaptic transmission synaptic plasticity synaptic morphology dendritic spine remodeling cognition

Histology and antitumor activity study of PTX-loaded micelle,a fluorescent drug delivery system prepared by PEG-TPP

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Chinese Chemical Letters 2019年第5期30卷 1083-1088页

作者： Huilan Li Jieming Li Xinyi He Bo Zhang Chunxia Liu Qifei Li Ying Zhu Wenlong Huang Wei Zhang Hai Qian Liang Ge Center of drug discovery State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China School of Pharmacy China Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of drug discovery for Metabolic Disease China Pharmaceutical UniversityNanjing 210009China department of Biochemistry and Molecular Biology Nanjing Medical UniversityNanjing 210029China

We synthesized PEG-TPP as carrier to encapsulate paclitaxel (PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size (152.1 ±1.2 nm) which is beneficial for enhanced permeability and retention (EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTX-loaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles (especially IC50 = 0.123 ± 0.035μmol/L of micelles and 0.298 ± 0.067μmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.

关键词： PEG-TPP Anticancer Micelles EPR Mitochondria

Identification of highly efficacious PROTACs targeting BRD4 against acute myeloid leukemia:Design,synthesis,and biological evaluations

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Chinese Chemical Letters 2023年第6期34卷 426-431页

作者： Aiping Chen Yue Zhong Yunxiao Liu Zhancheng Xie Hanyu Wu Wei Shi Wenlong Huang Renxiang Tan Hai Qian College of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Center of drug discovery State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of drug discovery for Metabolic Disease China Pharmaceutical UniversityNanjing 210009China

The abnormal activation of BRD4 accelerates the progression of acute myeloid leukemia(AML),developing more precise therapeutics to intervene BRD4 promise to be an excellent opportunity to avoid current limitations of chemotherapy in ***,a range of small-molecule PROTACs with the privileged 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one scaffold were rationally designed,which harbored different carbon or ethylenedioxy chains to degrade BRD4 mediated by the E3 ubiquitin ligase *** them,the most potential B24 exhibited remarkable BRD4 degradation and excellent anti-proliferative activities in MV4-11 cells,with values of DC_(50)and IC_(50)for 0.75 nmol/L and 0.4 nmol/L,respectively,which were better than the BRD4 inhibitor(+)-***,this compound could time-dependently degrade the target protein in the BRD4-,CRBN-,and proteasome-dependent ***,B24 dramatically decreased the level of proto-oncogene c-Myc,and induced cell apoptosis by arresting the cell cycle in G0/G1 phase,down-regulating Bcl-2 and up-regulating Bax to amplify apoptotic *** proof-of-concept study also highlighted the feasibility of BRD4-based PROTACs as a more powerful strategy against AML.

关键词： Acute myeloid leukemia BRD4 PROTACs Protein degradation Apoptosis

Synthesis, Crystal Structure and Biological Activity of 6-Arylmethyl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one Derivatives as Antitumor Agents

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Chinese Journal of Structural Chemistry 2019年第10期38卷 1691-1700,1610页

作者：高迪谭孝雨安甜甜于小飞金辄徐赫男孟庆国胡春 Key Laboratory of Structure-based drug Design & discovery Ministry of Education Shenyang Pharmaceutical University School of Pharmacy Yantai University

In order to explore the novel anti-tumor agents,ten 6-arylmethyl-3-aryl-777-thiazolo[3,2-b],2,4-triazin-7-ones were designed and synthesized,and the structures were characterized by ^1H-NMR,MS,IR and X-ray single-crystal diffraction *** biological activity results showed that the target compounds exhibited certain inhibitory activity of osteosarcoma cells *** 6a,6g and 6j exhibited more than 70%inhibition ratio at the concentration of 50μmol·L^-1,and especially,the IC5o value of compound 6j was 11.58μmol·L^-*** crystal of 6h was obtained and analyzed;some related weak interactions were *** molecular docking results showed that the target compounds were supposed to be ERK1/2 inhibitors.

关键词： thiazolo[3,2,-b]-1,2,4-triazine derivatives synthesis crystal structure antitumoractivity