检索结果-南通市图书馆

Dual PPAR delta/gamma agonist offer therapeutic potential for Alzheimer's disease

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第6期19卷 1175-1176页

作者： Ian Steinke Meenakshi Singh Rajesh Amin Department of drug discovery and Development Auburn University

The increasing incidence of Alzheimer’s disease(AD) in the aging population, indicates the critical need for the development of novel targeted molecular therapies for ameliorating AD pathology. Moreover, clinical and preclinical evidence demonstrates that peroxisomal proliferator activating receptors(PPAR) agonists regulate energy and lipid homeostasis in models of diabetes, as well as improve spatial memory in animal models of AD(Khan et al., 2019).

关键词：

Highly Aromatic Norditerpenoid Heterodimers and Monomers from Trigonostemon fragilis

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Engineering 2024年第7期38卷 144-154页

作者： Jun-Su Zhou Long Cheng Yuan Gao Zhan-Peng Ge Bin Zhou Jing-Ya Li Jin-Xin Zhao Jian-Min Yue State Key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Shandong Laboratory of Yantai drug discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantai 264117China

Four new norditerpenoid heterodimers with different dimerization patterns-namely,trigofragiloids A-C(denoted as compounds 1-3)and(+)-and(-)-trigofragiloid D(compound 4)-and three new phenanthrenone norditerpenoids-namely,trigofragiloids E-G(compounds 5-7)-were isolated from Trigonostemon *** 1 and 2 feature a novel heterodimeric carbon skeleton formed by the conjugation of a tetra-norditerpenoid and an ennea-norditerpenoid;they have been identified as class 2 atropisomers by means of quantum chemical *** 3 is an unprecedented phenylpropanoid-norditerpenoid adduct with a new dimerization ***(+)-and(-)-4 are the first example of S-shaped 1,4-dioxane-fused norditerpenoid *** by the structure elucidation of compound 4,two co-occurring analogues,actephilol A and epiactephilol A,were structurally revised as a pair of geometrical isomers and were identified as two pairs of enantiomers,(+)-and(-)-8 and(+)-and(-)-9,*** structures were characterized using a combined ***,compound 7 exhibits remarkable adenosine triphosphate-citrate lyase(ACLY)inhibition with a halfmaximal inhibition concentration(IC50)value of(0.46±0.11)lmol·L^(-1),as active as the positive control BMS-303141,and a molecular docking study offers deep insight into the interaction between compound 7 and ACLY.

关键词： Norditerpenoid heterodimer Trigonostemon fragilis Euphorbiaceae Trigofragiloid Structural revision Adenosine triphosphate-citrate lyase(ACLY) inhibitory activity

Recent advances in the culture-independent discovery of natural products using metagenomic approaches

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2024年第2期22卷 100-111页

作者： SHEN Yiping LIU Nan WANG Zongqiang Laboratory of Microbial drug discovery China Pharmaceutical UniversityNanjing 211198China

Natural products derived from bacterial sources have long been pivotal in the discovery of drug ***,the cultivation of only about 1%of bacteria in laboratory settings has left a significant portion of biosynthetic diversity hidden within the genomes of uncultured *** in sequencing technologies now enable the exploration of genetic material from these metagenomes through culture-independent *** approach involves extracting genetic sequences from environmental DNA and applying a hybrid methodology that combines functional screening,sequence tag-based homology screening,and bioinformatic-assisted chemical *** this process,numerous valuable natural products have been identified and synthesized from previously uncharted metagenomic *** paper provides an overview of the recent advancements in the utilization of culture-independent techniques for the discovery of novel biosynthetic gene clusters and bioactive small molecules within metagenomic libraries.

关键词： Metagenomics Culture-independent approach Natural product Functional screening Sequence tag-based homology screening Syn-BNP

Nuance of inward rectifying potassium(Kir) channel dysfunctions in neurodegenerative diseases

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第6期19卷 1195-1196页

作者： Benjamin Garland Linlin Ma Griffith Institute for drug discovery & School of Environment and Science Griffith University

Neurodegenerative disorders are highly prevalent and diverse in nature. Their manifestation largely depends on the cell types involved, with aberrant inflammatory episodes progressively inducing a constellation of phenotypes that are classified into specific diseases based on their neuropathological traits. The two most prevalent neurodegenerative diseases worldwide,

关键词： K-ATP CHANNELS PARKINSONS-DISEASE MODEL

Development of SV2A Ligands for Epilepsy Treatment:A Review of Levetiracetam,Brivaracetam,and Padsevonil

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Neuroscience Bulletin 2024年第5期40卷 594-608页

作者： Peng-Peng Wu Bi-Rong Cao Fu-Yun Tian Zhao-Bing Gao center for Neurological and Psychiatric Research and drug discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China Zhongshan Institute for drug discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan528400China

Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications(ASMs).Although dozens of ASMs are available in the clinic,approximately 30%of epileptic patients have medically refractory seizures;other limitations in most traditional ASMs include poor tolerability and drug-drug ***,there is an urgent need to develop alternative ***(LEV)is a first-line ASM that is well tolerated,has promising efficacy,and has little drug-drug *** it is widely accepted that LEV acts through a unique therapeutic target synaptic vesicle protein(SV)2A,the molecular basis of its action remains *** so,the next-generation SV2A ligands against epilepsy based on the structure of LEV have achieved clinical *** review highlights the research and development(R&D)process of LEV and its analogs,brivaracetam and padsevonil,to provide ideas and experience for the R&D of novel ASMs.

关键词： Levetiracetam Epilepsy Antiseizure medications Synaptic vesicle protein 2A Brivaracetam Padsevonil

AI enhances drug discovery and development

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

National Science Review 2024年第3期11卷 52-54页

作者： Fang Bai Shiliang Li Honglin Li Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech University Lingang Laboratory Innovation center for AI and drug discovery East China Normal University

The advent of the third wave of artificial intelligence(AI) heralds a new era in drug discovery. AI-powered techniques can be characteristic of identifying features that are difficult for humans to interpret from big ...

关键词：

Sigmatropic rearrangements of B(MIDA)-propargylic alcohols towards the diverse synthesis of α-functionalized organoborons

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Science China Chemistry 2024年第2期67卷 568-575页

作者： Jiasheng Qian Li-Cai Liu Zhi-Hao Chen Yuan Liu Yin Li Qingjiang Li Honggen Wang Guangdong Key Laboratory of Chiral Molecule and drug discovery School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou510006China

α-Functionalized organoborons are useful building blocks and key structural elements in functional *** previous synthesis relied on the famous Matteson reaction or the late-stage borylative modification of alkynes or ***,the synthetic transformation of borylated building blocks offers another useful strategy and is currently actively *** report herein that B(MIDA)-propargylic alcohols(BPAs) are a useful type of borylated building *** two complementary functional group handles(alkyne and hydroxyl) in close proximity,the redox-neutral [3,3] and [2,3] sigmatropic rearrangements of BPAs allow the efficient synthesis of several types of α-functionalized boronates,including α,β-unsaturated acylborons,α-S/P-substituted allenylborons,boryl-substituted thiazoles and a borylated α,β-unsaturated hydrazine,some of which are otherwise challenging targets using other synthetic methods.

关键词： organoboron diverse synthesis sigmatropic rearrangement heteroarene amide

维普期刊数据库

Click chemistry and natural products

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2024年第2期22卷 97-99页

作者： ZHANG Chen WU Jianbing ZHANG Yihua HUANG Zhangjian 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 Pathogenesis Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiang Key Laboratory of Natural Medicines Active Components and Drug Release TechnologySchool of PharmacyXinjiang Medical UniversityUrumqi 830054China

The 2022 Nobel Prize in Chemistry was awarded to American scientists Carolyn Bertozzi,*** Sharpless,and Danish scientist Morten *** for their contributions to the development of click chemistry and bioorthogonal chemi... 详细信息

关键词： Click chemistry Natural product Target identification drug discovery

Design,synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2024年第5期35卷 287-289页

作者： Wenyi Mei Lijuan Xie Xiaodong Zhang Cunjian Shi Fengzhi Wang Qiqi Fu Zhenjiang Zhao Honglin Li Yufang Xu Zhuo Chen Shanghai Key Laboratory of New drug Design State Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Innovation center for AI and drug discovery East China Normal UniversityShanghai 200062China Lingang Laboratory Shanghai 200031China

Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological *** clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole(NBD)*** them,5c exhibited similar anti-proliferative activity with UA against HCT116 cells(half maximal inhibitory concentration(IC_(50))=9.21±0.50μmol/L).Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent ***,5c was found to localize in endoplasmic reticulum(ER),lysosomes,and mitochondria,but not in nucleus of HCT116 cells by confocal microscopy *** MOA proved that UA induced autophagy with a unique intracellular distribution mechanism involving ER and *** all,our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.

关键词： Pentacyclic triterpenoid Ursolic acid Fluorescent derivatives Autophagy Apoptosis

维普期刊数据库