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Traditional Medicine research 2023年第7期8卷 11-23页

作者： Di Liang Wei-Mei Zhang Xu Liang Hong-Yue Tian Xue-Min Zhang Xia Li Wen-Yuan Gao tianjin key laboratory for Advanced drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300193China key laboratory of Advanced Chinese Medicine Resources research Enterprises Tianjin 300402China college of pharmacy Qinghai Minzu UniversityQinghai 810007China

Andrographolide is the main active ingredient of Andrographis paniculata(Burm.f.)Nees,known as“natural antibiotic”.Here,for the purpose of discovering a more efficient,low-cost extraction and separation method,the research status of andrographolide was *** present,researches only take extraction rate as the only index to optimize extraction parameters,but ignores the importance of extraction *** is usually meaningless to blindly pursue the extraction rate without considering the difficulty and cost of subsequent ***,factors affecting extraction selectivity such as solvent choice,temperature and physicochemical effects caused by extraction technique itself,are first *** extraction techniques for andrographolide were discussed by comparing the selectivity,efficiency and cost of *** separation procedures of andrographolide such as decolorization,impurity removal,crystallization,membrane separation,solid-phase extraction and partition chromatography and their challenges and possible strategies are also *** is hoped that this review can provide guidance for researchers who are committed to advancing the field of andrographolide extraction and purification.

关键词： andrographolide extraction techniques extraction selectivity separation

Correlation Analysis between Visceral Manifestation Theories on Xuanfa and Effect of Adrenergic Receptors

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Chinese Herbal Medicines 2014年第2期6卷 85-92页

作者： Gang Bai Yuan-yuan Hou Min Jiang Jie Gao State key laboratory of Medicinal Chemical Biology College of Pharmacy Nankai University tianjin key laboratory of molecular drug research Nankai University

Chinese visceral manifestation theory states that lung dominates qi,regulates breathing,and governs Xuanfa（dispersing）and Sujiang（descending）.Clarifying this theory with modern physiological and pathological knowledge has been considered as an important part of complementary and alternative medicine *** studies found that most Xuanfa drugs contained pharmacodynamic ingredients related to adrenergic receptors（ARs）signal *** association of Xuanfa,with the control of breath movement,nutrient transfer,spreading heat to regulate temperature,and helping the heart control blood circulation,coincides with the physiological function of organs dominated by ARs-regulated sympathetic postganglionic ***,we hypothesize that Xuanfa is closely related to ARs-regulated signal *** modern biological knowledge,we tried to evaluate and expound the correlation between the molecular mechanisms of modern physiology or pathology and Xuanfa or Sujiang ***,the research and development of modern drugs should fully expect the guidance from Chinese visceral manifestation theory,and the application of this principle will guide the prevention and clinical treatment of a variety of refractory diseases caused by a change in environment,climate,or lifestyle.

关键词： adrenergic receptor molecular mechanism Xuanfa(dispersing) Sujiang(descending) sympathetic nerves

Enantioselective Synthesis of Benzimidazole Atropisomers Featuring a N-N Axis

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Chinese Journal of Chemistry 2024年第7期42卷 711-718页

作者： Fang-Bei Ge Qi-Kun Yin Chuan-Jun Lu Xuan Xuan Jia Feng Ren-Rong Liu college of Chemistry and Chemical Engineering Qingdao UniversityQingdaoShandong 266071China School of pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationYantai UniversityYantaiShandong 264005China

Atroposelective synthesis of N-N atropisomers is an emerging area but remains underexplored;in particular,the synthesis of N-N benzimidazole atropisomers is still ***,the first enantioselective synthesis of N-N benzimidazole atropisomers via the palladium-catalyzed de novo construction of benzimidazole skeleton is *** readily available palladium catalyst and biphosphine ligand,a broad range of nonbiaryl benzimidazole and indole-benzimidazole atropisomers were conveniently ac-cessed in high yields and with excellent ***,these N-N benzimidazole atropisomers showed great anti-tumor activity and selectivity to breast cancer MCF-7 *** simple catalytic system,broad substrate scope,high enantioselectivi-ty,and good bioactivity make this approach highly attractive.

关键词： Asymmetric synthesis Atropisomerism Palladium Benzimidazole Antitumor

Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2306-2325页

作者： Liang Han Chen Jiang Jiangsu key laboratory of Neuropsychiatric Diseases research College of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China key laboratory of Smart drug Delivery Ministry of EducationState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 200032China

Bloode-brain barrier(BBB)strictly controls matter exchange between blood and brain,and severely limits brain penetration of systemically administered drugs,resulting in ineffective drug therapy of brain ***,during the onset and progression of brain diseases,BBB alterations evolve *** this review,we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer’s disease,Parkinson’s disease,epilepsy,stroke,traumatic brain injury and brain *** advances on optimization of small molecules for BBB crossing and non-systemic administration routes(e.g.,intranasal treatment)for BBB bypassing are not included in this review.

关键词： Blood-brain barrier Brain diseases Brain-targeting drug delivery systems Nanoparticles

Chemical–biological approaches for the direct regulation of cell–cell aggregation

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Aggregate

Aggregate 2022年第2期3卷 33-49页

作者： Jia-Yi Ma Ya-Xin Wang Yan Huang Yi Zhang Yun-Xi Cui De-Ming Kong State key laboratory of Medicinal Chemical Biology Nankai UniversityTianjinP.R.China School of pharmacy Binzhou Medical UniversityYantaiShandongP.R.China college of Life Sciences Nankai UniversityTianjinP.R.China tianjin key laboratory of Biosensing and molecular Recognition Research Centre for Analytical SciencesCollege of ChemistryNankai UniversityTianjinP.R.China

Cell–cell aggregation is one of the most well-known modes of intercellular *** aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of *** the past decades,cell–cell aggregation-related bioprocesses and molecular mechanisms have attracted enormous interest from scientists in biology,and *** have developed a series of strategies to artificially regulate cell–cell aggregation through chemical–biological *** date,not only the chemical reagents such as coordination compounds and polymers but also the biomacromolecules such as proteins and nucleic acids,are employed as the“cell glue”to achieve the control of the cell *** it is meaningful to review the recent advances of the chemical–biological approaches in cell–cell aggregation *** this review,we discuss the mechanisms and features of recently developed strategies to control cell–cell *** introduce molecules and designs relying on chemical reactions and biological conjugations respectively,and talk about their advantages and suitable applications.A perspective on the challenges in future applications in cell manipulation and cell-based therapy is also *** expect this review could inspire innovative work on manipulating cell–cell aggregation and further modulate cell–cell interactions in the research of bio/chemical fields.

关键词： cell-cell aggregation molecular glue precise regulation

Potential use of a dried saliva spot(DSS)in therapeutic drug monitoring and disease diagnosis

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Journal of Pharmaceutical Analysis 2022年第6期12卷 815-823页

作者： Yu Han Xi-Ling Li Minghui Zhang Jing Wang Su Zeng Jun Zhe Min key laboratory of Natural Medicines of the Changbai Mountain Ministry of EducationDepartment of Pharmaceutical AnalysisCollege of PharmacyYanbian UniversityYanjiJilin133002China Institute of drug Metabolism and Pharmaceutical Analysis Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China

In recent years,scientific researchers have increasingly become interested in noninvasive sampling methods for therapeutic drug monitoring and disease *** a result,dried saliva spot(DSS),which is a sampling technique for collecting dried saliva samples,has been widely used as an alternative matrix to serum for the detection of target *** the DSS method with a highly sensitive detection instrument improves the efficiency of the preparation and analysis of biological ***,dried blood spots,dried plasma spots,and dried matrix spots,which are similar to those of the DSS method,are *** with alternative biological fluids used in dried spot methods,including serum,tears,urine,and plasma,saliva has the advantage of convenience in terms of sample collection from children or persons with *** review aims to provide integral strategies and guidelines for dried spot methods to analyze biological samples by illustrating several dried spot ***,we summarize recent advancements in DSS methods from June 2014 to March 2021 and discuss the advantages and disadvantages of the key aspects of this method,including sample preparation and method ***,we outline the challenges and prospects of such methods in practical applications.

关键词： Human saliva Dried saliva spot Therapeutic drug monitoring Disease diagnosis

Natural products inspired[3+2]cycloaddition enables efficient construction of hydroxylated tetrahydrofuran acetals and concise syntheses of lignans

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Science China Chemistry 2024年第7期67卷 2306-2313页

作者： Dong-Yue Cai Weiming Shi Zhao-Hui Jin Zhi-Xiang Yu Jin-Xin Zhao Jian-Min Yue State key laboratory of drug research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Beijing National laboratory for molecular Sciences(BNLMS) Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of ChemistryPeking UniversityBeijing 100871China

Mimicking biosynthetic pathways of hongkonoids led to the development of a new Cu(Ⅰ)-catalyzed[3+2]cycloaddition ofα-hydroxyketone andβ-keto enol ethers,affording tetrahydrofuran acetals in a highly diastereoselective manner and 100%atom *** studies on the mechanism disclosed a concerted but asynchronous Michael addition/aldol *** the same importance,this methodology provides a practical biomimetic approach for one-step construction of the dibenzylbutyrolactol lignan backbone starting from two phenyl propane derivatives,opening up a powerful new approach for lignan synthesis,which is showcased by succinct total syntheses of two biologically important aryltetralin-type lignans,β-apopicropodophyllin and *** the mild and operationally simple conditions,the developed chemistry might have a promising prospect in potential industrial applications.

关键词： [3+2]cycloaddition transition-metal catalysis tetrahydrofuran lignans natural products

Tetramethylpyrazine nitrone improved mitochondrial dysfunction, downregulated α-synuclein, and reduced neurodegeneration in Parkinson disease models

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中国药理学与毒理学杂志 2019年第10期 843-844页

作者： GUO Bao-jian ZHENG Cheng-you QIU Xiao-ling ZHANG Zai-jun Institute of New drug research and Guangzhou key laboratory of Innovative Chemical drug research in Cardiocerebrovascular Diseases Jinan University College of Pharmacy

OBJECTIVE The peroxisome proliferatoractivated receptor γ co-activator 1α(PGC-1α) and nuclear factor(erythroid-derived 2)-like 2(Nrf2) are key regulators controlling antioxidant defense, mitochondrial biogenesis and cellular proteostasis. Dysfunction of any of these processes has been implicated in the pathogenesis of Parkinson disease(PD). Activation of PGC-1α/Nrf2 might improve mitochondrial dysfunction, promote α-synuclein(α-syn) clearance, and attenuate degeneration of nigral dopaminergic neurons in PD. To test this, we used tetramethylpyrazine nitrone(TBN), a potent free radical scavenger, to activate PGC-1α/Nrf2 pathway. METHODS 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP)-induced mouse model, unilateral intrastriatal injection of 6-hydroxydopamine(6-OHDA)-induced rat model, and transgenic mice overexpression of human A53 T mutant α-synuclein were used to evaluate TBN's therapeutic efficacy and to explore its mechanisms of action. RESULTS TBN protected against 1-methyl-4-phenylpyridinium(MPP+) and 6-OHDA insult in cultured primary midbrain neurons. TBN promoted α-syn clearance by autophagy and proteasomal pathways in the cell models overexpressed human A53 T mutant α-syn. In MPTP-treated mouse and unilateral 6-OHDA-lesioned rat, as well as in α-syn transgenic mouse model, TBN improved motor impairment, increased survive of nigra dopaminergic neurons, and elevated striatal dopamine level, while decreased the products of oxidative ***, TBN down-regulated α-syn level in the brain and serum of α-syn transgenic mice. These improvements in vitro and in vivo were associated with activation of PGC-1α/Nrf2 signal pathway, resulting in reduced oxidative stress, enhanced mitochondrial function, and increased protein clearance. CONCLUSION Our work demonstrates that activation of PGC-1α/Nrf2 by TBN can maintain the survival of nigral dopaminergic neurons, and might be disease-modifying in PD models, providing the critical rationale for further devel

关键词： tetramethylpyrazine nitrone Parkinson disease peroxisome proliferator-activated receptor γ co-activator 1α nuclear factor(erythroid-derived 2)-like 2 α-synuclein

Recent Advances in Electrochemical Oxidation to Construct C–O Bonds

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Transactions of tianjin University 2022年第6期28卷 482-505页

作者： Lei Zhan Wan-Jie Wei Cai-Nai Jiang Lei Gao Xian-Li Ma Guangxi key laboratory of drug Discovery and Optimization Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability EvaluationSchool of PharmacyGuilin Medical UniversityGuilin 541004China

C–O bonds are widely found in pharmaceuticals and natural products and have various pharmacological ***,developing eff ective strategies for constructing compounds containing C–O bonds has become a research hotspot among *** electrochemical synthesis is a green,mild,and effi cient strategy that shows great potential in the synthesis of compounds containing C–O *** review introduces the reactions of compounds containing C–O bonds recently constructed by electrochemical methods and expounds the corresponding reaction mechanism to provide a reference for applying such reactions in organic synthesis.

关键词： Organic electrochemistry C–O bond Green synthesis

Design,synthesis and evaluation of PPAR gamma binding activity of 2-thioxo-4-thiazolidinone derivatives

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Chinese Chemical Letters 2015年第1期26卷 63-68页

作者： Li Zhou Ye Zhong Meng-Zhu Xue Dong Kuang Xian-Wen Cao Zhen-Jiang Zhao Hong-Lin Li Yu-Fang Xu Rui Wang Shanghai key laboratory of New drug Design State Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science and Technology

We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor γ（PPARγ） binding *** the biological assays,compounds 18 and 38 were highlighted with K_i values of 12.15 nmol/Land 14.46 nmol/L,*** structure-activity relationship（SAR） was analyzed to screen privileged structural ***,molecular fitting of these compounds onto the approved drug Rosightazone in the PPARγligand binding domain was performed to elucidate the SAR and explore potential receptor-ligand *** results demonstrate that the 2-thioxo-4-thiazolidinones can be considered as new promising molecular probes with excellent binding activities to PPARγ.

关键词： 2-Thioxo-4-thiazolidinone Peroxisome proliferator activated receptorγ Binding activities SAR molecular docking