检索结果-内蒙古大学图书馆

Novel Pleuromutilin Derivatives Conjugated with Phenyl-Sulfide and Boron-Containing Moieties as Potent Antibacterial Agents Against Antibiotic-Resistant Bacteria

SSRN

引用

SSRN 2024年

作者： Luo, Xinyu Wu, Guangxu Feng, Jing Zhang, Jie Fu, Hengjian Yu, Hang Han, Zunsheng Nie, Wansen Zhu, Zihao Liu, Bo Pan, Weidong Li, Beibei Wang, Yan Li, Tianlei Zhang, Wenxuan Wu, Song State Key Laboratory of Bioactive Substance and Function of Natural Medicines Department of New Drug Research and Development Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing100050 China State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Guiyang550014 China Shanghai Veterinary Research Institute Chinese Academy of Agricultural Science Shanghai200241 China Guizhou University China

In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b displayed significantly bactericidal activity and low spontaneous resistance frequency as well as high stability in liver microsomes of rats and humans. Compound 16b also exhibited promising antibacterial activities and tolerance in mouse models. Our data highlight the potential of conjugated pleuromutilin derivatives as valuable agents against drug-resistant bacteria. © 2024, The Authors. All rights reserved.

关键词： Sulfur compounds

来源：评论

学校读者我要写书评

暂无评论

Regulating the Physical and Chemical Properties of Gefitinib and its Positional Isomer Through Salt Formation

SSRN

引用

SSRN 2024年

作者： Li, Shuang Zhou, Xia Dong, Wenjing Liu, Meiru Wang, Wenwen Zhao, Zhehui Zhang, Li Yang, Dezhi Lu, Yang Du, Guanhua Beijing Key Laboratory of Polymorphic Drugs Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing100050 China State Key Laboratory of Bioactive Substances and Function of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing100050 China Ningxia Institute for Drug Control Yinchuan750001 China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing100050 China Beijing Key Laboratory of Drug Targets Identification and Drug Screening National Center for Pharmaceutical Screening Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing100050 China China Pharmaceutical University China

The structural differences between Gefitinib (GFN) and its positional isomers, specifically N-(2-Fluoro-3-chlorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine(ISOGFN), appear minimal on a two-dimensional level. Despite their similar crystallization packing styles, the physical and chemical properties of the two solid states differ significantly, obstructing the development of the isomer into pharmaceutical drugs. Can cocrystallization with an identical ligand bridge this gap? In this study, we first prepared crystal of the GFN positional isomer. We then synthesized two distinct salts of GFN and its isomer using fumaric acid (FA, pKa:3.03) as the ligand, comparing the physicochemical properties of these samples. X-ray diffraction was conducted to characterize these crystals, alongside vibrational spectrum and thermal analysis. Additionally, their dissolution and permeability properties were evaluated to identify and summarize similarities and differences. Theoretical computational studies, including crystal packing similarity, proton transfer, Gibbs free energy, and interaction energy, were employed to elucidate the differences in properties from the structural and energy perspectives. The results indicated that introducing FA diminished the differences in properties between GFN and its positional isomer, especially in terms of solubility, permeability, thermostability, and packing similarity. For the isomer, its improvement in permeability after salt formation, which overcomes its shortcoming, providing a valuable reference for isomer drug research and development. © 2024, The Authors. All rights reserved.

关键词： Ligands

来源：评论

学校读者我要写书评

暂无评论

Rg1 improves LPS-induced Parkinsonian symptoms in mice via inhibition of NF-κB signaling and modulation of M1/M2 polarization

引用

中国药理学报（英文版） 2020年第4期41卷 523-534页

作者： Jia-qi Liu Ming Zhao Zhao Zhang Li-yuan Cui Xin Zhou Wei Zhang Shi-feng Chu Da-yong Zhang Nai-hong Chen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica and Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China China Pharmaceutical University Nanjing 210009 China Beijing Hospital Beijing 100730 China Institute of Chinese Integrative Medicine Hebei Medical University Shijiazhuang 050017 China

Ginsenoside Rg1 is one of the most active ingredients in ginseng,which has been reported to protect dopaminergic neurons and improve behavioral defects in MPTP model,6-OHDA model and rotenone ***,it is unclear whether Rg1 exerted neuroprotection in LPS-induced sub-acute PD *** this study,we investigated the neuroprotective effect of Rg1 in the subacute PD mouse model and explored the related ***1 (10,20,40 mg·kg-1·d-1) was orally administered to mice for 18 days.A sub-acute PD model was established in the mice through LPS microinjection into the substantia nigra (SN) from D8 to *** found that Rg1 administration dose-dependently inhibited LPS-induced damage of dopaminergic neurons and activation of glial cells in the substantia nigra pars compacta (SNpc).The neuroprotective effects of Rg1 were associated with the reduction of pro-inflammatory cytokines and the improvement of anti-inflammatory cytokines and neurotrophin in the ***1 shifted the polarization of microglia towards the M2 phenotype from M1,evidenced by decreased M1 markers (inducible NO synthase,CD16,etc.) and increased M2 markers (arginase 1 (Arg1),CD206,etc) in the ***,Rg1 administration markedly inhibited nuclear translocation of NF-κB in midbrain *** conclusion,Rg1 protects PD mice induced by continuous LPS injection by inhibiting the nuclear entry of NF-κB and regulating the polarization balance of microglia,shedding new light on a disease-modifying therapy of PD.

关键词： Parkinson's disease ginsenoside Rg1 neuroinflammation lipopolysaccharide microglia polarization NF-κB

来源：评论

学校读者我要写书评

暂无评论

A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models

引用

Acta Pharmaceutica Sinica B 2020年第2期10卷 276-288页

作者： Jing Jin Nina Xue Yuan Liu Rong Fu Mingjin Wang Ming Ji Fangfang Lai Jinping Hu Xiaojian Wang Qiong Xiao Xiaoying Zhang Dali Yin Liping Bai Xiaoguang Chen Shuan Rao State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China Department of Thoracic Surgery Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Quality Research in Chinese Medicine Macao Institutefor Applied Research in Medicine and HealthMacao University of Science and TechnologyTaipaMacao SAR 999078China

Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of *** understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations ***,we showed that IMMH002,a novel orally active S1 P1 modulator,desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and *** different psoriasis animal models,we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PAS I score and pathological injure ***,IMMH002 regulated CD3+T lymphocytes re-distribution by inducing lymphocytes’homing,thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the *** results suggest that the novel SIP1 agonist,IMMH002,exert extraordinary capacity to rapidly modulate T lymphocytes distribution,representing a promising drug candidate for psoriasis treatment.

关键词： S1P1 S1P1 agonist IMMH002 Lymphocyte Psoriasis

来源：评论

学校读者我要写书评

暂无评论

Pathophysiology and system biology of rat c-BSA induced immune complex glomerulonephritis and pathway comparison with human gene sequencing data

引用

International Immunopharmacology 2022年第0期109卷 108891页

作者： Wu, Haijie Jia, Binghan Zhao, Xiaodi Zhang, Haoyu Li, Zhaojun Wang, Weida Chen, Xiaoguang Zhang, Sen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Department of Pharmacology Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China School of Undergraduate QILU Medical University Shandong Province Zibo 255213 China

Immune-complex glomerulonephritis (ICGN) is a major cause of nephrotic syndrome in adults and children. Cationic BSA (c-BSA) intravenous injection could produce significant albuminuria within a short time, and is a suitable in vivo experimental animal model to investigate the pathophysiology of ICGN and for drug screening, but lack of thorough study to clarify its dynamic pathophysiological alteration so far, as well as detailed changes in mRNA and LncRNA levels. The purpose of this study is to investigate the dynamic alteration in renal function, lipid metabolism and histopathology during the progress of c-BSA induced ICGN. RNA sequencing was used to identified differentially expressed mRNA and LncRNA in kidney cortex of ICGN. Results demonstrated that c-BSA induced ICGN model could completely exhibit clinical features of immune-mediated nephrotic syndrome with gradual declining renal function, and increased albuminuria and deteriorated histopathological injuries. The correlation analysis suggested that complement activation was the most key element in mediating of ICGN. RNA sequencing using rat kidney tissues combined with Gene Expression Omnibus (GEO) data of human glomerulonephritis showed the most enriched KEGG pathways in ICGN were Toll-like receptor signaling pathway, B cell receptor and Focal adhesion. The differential lncRNAs in ICGN rats were also screened, and the lncRNA-mRNA co-expression network was constructed to clarify lncRNA role in molecular mechanism of ICGN progression. Their human homogenous lncRNAs were also identified, such as ST3GAL5-AS1 and DIO3OS, which provide the potential lncRNA targets to treat ICGN. All the differential LncRNAs in ICGN kidneys caused by MMF were also identified and provided another possible pharmacological mechanism of MMF through lncRNA regulation. In summary, the current study firstly described the dynamic physiological changes of c-BSA induced ICGN, identified most key KEGG pathways, and provided lncRNA-mRNA regulat

关键词： Cationic BSA (C-BSA) Complement activation Gene Expression Omnibus (GEO) data Immune-complex glomerulonephritis (ICGN) lncRNA-mRNA co-expression network RNA sequencing

来源：评论

学校读者我要写书评

暂无评论

Discovery of Novel Photoswitchable Pd-L1 Inhibitors Toward Precision Cancer Immunotherapy

SSRN

引用

SSRN 2024年

作者： Zhang, Yan Guan, Jichen Qi, Haixiang Huang, Lei Tian, Hua Liu, Junyi Lin, Songwen Dong, Yi Lai, Fangfang Xu, Heng State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing100050 China Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing100050 China CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery Institute of Materia Medica Chinese Academy of Medical Sciences Beijing100050 China

Small molecule PD-L1 inhibitors have emerged as a promising therapeutic approach in cancer immunotherapy. In this work, we present a novel series of photoswitchable PD-L1 inhibitors developed through a design strategy that incorporates an azo group into biphenyl derivatives. The lead compound 13a demonstrates effective trans-cis isomerization upon irradiation with 365nm/435nm wavelength light, leading to distinct potency in disrupting PD-1/PD-L1 interaction. Notably, compound 13a in the PSSdark exhibits superior efficacy in rescuing T cell inhibition, suppressing cancer cell proliferation, reducing PD-L1 expression on the cancer cell and promoting PD-L1 degradation as compared to the PSS365. Overall, compound 13a represents the first example of a photoswitchable PD-L1 inhibitor, opening up a new avenue towards precision cancer immunotherapy. © 2024, The Authors. All rights reserved.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Hige namine as a Potential Pharmacologic Stress Age nt in the Detection of Coro nary Artery Disease

引用

Chinese Medical Sciences Journal 2022年第3期37卷 275-281,I0014页

作者： Nana Zhang Zijian Li Haibo Zhu Unstitute of Food Scienee and Technology Chinese Academy of Agricultural SciencesBeijing 100050China Institute of Vascular Medicine Peking University Third HospitalKey Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of HealthKey Laboratory of Molecular Cardiovascular Sciences Ministry of Educationand Beijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100050China State Key Laboratory for Bioactive Substances and Functions of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation StudyInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Myocardial perfusion imaging(MPI) is valuable for the diagnosis,prognosis,and management of coronary artery disease(CAD).The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic ***,these agents have contraindications and may cause adverse effects in some ***,other stress agents feasible for more patients are ***(HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial *** also has a promising value in MPI for the detection of CAD in preclinical and clinical *** review summarizes the application of HG on MPI,including its mechanism of action,stress protocol,efficacy,and safety.

关键词： coronary artery disease higenamine myocardial perfusion imaging stress agent

来源：评论

学校读者我要写书评

暂无评论

Rhodium-catalyzed site-selective cross-couplings of indoles and pyridotriazoles through carbene insertion

引用

Chinese Chemical Letters 2025年第7期36卷

作者： Tian, Hua Yang, Xin Shi, Ge Xu, Heng Dong, Yi State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery Chinese Academy of Medical Sciences Beijing 100050 China

The switchable cross-coupling of indoles and pyridotriazoles through carbene insertion at C2- or C3-positon has been developed in this paper. This highly site-selective C−H carbenoid functionalization is determined by... 详细信息

The switchable cross-coupling of indoles and pyridotriazoles through carbene insertion at C₂- or C₃-positon has been developed in this paper. This highly site-selective C−H carbenoid functionalization is determined by both the Rh-catalyst species and auxiliary groups. [Cp*RhCl₂]₂ and coordinating pyrimidyl group direct the C−H carbenoid functionalization to occur at the C₂-position, while Rh₂OAc₄ and non-coordinating benzyl group lead the reaction to occur at the C₃-position of the indoles. This regioselective C−H functionalization strategy is of significant importance for the discovery of indole drugs. © 2025

关键词： Carbene insertion Cross-couplings Pyridotriazoles Rhodium-catalyzed Site-selective

来源：评论

学校读者我要写书评

暂无评论

TLR4 deficiency has a protective effect in the MPTP/probenecid mouse model of Parkinson's disease

引用

中国药理学报（英文版） 2019年第12期40卷 1503-1512页

作者： Qian-hang Shao Ying Chen Fang-fang Li Shuo Wang Xiao-ling Zhang Yu-he Yuan Nai-hong Chen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China College of Pharmacy Hunan University of Chinese Medicine Changsha 410208 China

Parkinson's disease (PD) is a multifactorial disorder characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (LBs) consisting of misfolded α-synuclein *** etiology of PD is still not clear but systemic inflammation is proved to trigger and exacerbate DA neurons ***-like receptor 4 (TLR4) is a pattern-recognition receptor (PRR) and plays a major role in promoting the host ***4-mediated signal pathways induce the release of many inflammatory *** is reasonable to hypothesize that TLR4 is the mediator in microglia contributing to the damage of DA neurons in the *** this study,we evaluated the role of TLR4 in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid mouse *** TLR4-deficient and wild-type (WT) mice were injected with probenecid (250 mg/kg,i.p.) followed by injection of MPTP (25 mg/kg,s.c.) every 4 days for 10 *** D43 to D47,the behavioral performance in pole test and wire hang test was *** the mice were euthanized,and SN and striatum were dissected out for biochemical *** showed that compared with MPTP-treated WT mice,TLR4 deficiency significantly attenuated MPTP-induced motor deficits and TH-protein expression reduction in SNpc and striatum,suppressed MPTP-induced α-synuclein abnormality and neuroinflammation mediated through oxidative stress,glial activation,NF-KB and the NLRP3 inflammasome signaling *** findings highlight the neuroprotective effect of TLR4-pathways in the chronic MPTP-induced PD mouse model.

关键词： Parkinson's disease Toll-like receptor 4 MPTP/probenecid mouse model α-synuclein oxidative stress glial activation NF-KB neuroinflammation

来源：评论

学校读者我要写书评

暂无评论

Author Correction: CB2 receptor activation inhibits the phagocytic function of microglia through activating ERK/AKT-Nurr1 signal pathways

引用

Acta pharmacologica Sinica 2024年第10期45卷 2228页

作者： Qi-Wen Han Qian-Hang Shao Xiao-Tong Wang Kai-Li Ma Nai-Hong Chen Yu-He Yuan State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China. Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical College Kunming 650118 China. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China. chennh@***. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China. yuanyuhe@***.

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：