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Chinese Journal of Structural Chemistry 2022年第2期41卷 132-140,I0011页

作者： LIU Ju WU Shuang WANG Huan dU Si-Yuan LI Zhen SHEN Ji-Wei CHEN Ye dING Shi College of Pharmacy of liaoning University Shenyang 110036China API engineering Technology research center of liaoning province Shenyang 110036China small molecular targeted drug r&d engineering research center of liaoning province Shenyang 110036China

A series of 2,4-diarylaminopyrimidine derivatives containing pyridine structure were designed and *** crystal structures of compounds 5d and 5e were obtained from X-ray *** crystal structure of 5d (C_(25)H_(20)Cl FN_(6)O_(2)) belongs to the monoclinic system,space group P2_(1)/c with a=11.0500(10),b=18.3045(17),c=13.5646(9)?andβ=122.806(5)°.5e (C_(25)H_(19)Cl F_(2)N_(6)O_(2)) is of monoclinic system,space group P2_(1)/c with a=10.9998(18),b=18.517(3),c=13.6355(16)?andβ=123.315(9)°.The bioassay results showed all of the target compounds exhibited potential antiproliferative activities against MKN-45,HT-29,A549,K562 and GIST882 cell *** them,compounds 5a,5c and 5e exhibited remarkable inhibitory activities against GIST882,K562 and A549 cell lines with IC_(50 )values of 0.68,0.38 and 0.60μM,respectively,which were comparable to that of the positive control foretinib.

关键词： pyrimidine pyridine synthesis X-ray diffraction antitumor activity

Nanocarrier-mediated sirNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural regeneration research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie ren Institute of disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for disaster Medicine Technology TianjinChina Henan Medical Key Laboratory for research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical center of Tissue engineering and regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina Institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering rNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of sirNAs,discussing the advantages,challenges,and future *** principle,sirNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,sirNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering sirNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified sirNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

rapid discovery of two unprecedented meroterpenoids from daphne altaica *** molecular networking integrated with MolNetEnhancer and Network Annotation Propagation

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Chinese Chemical Letters 2024年第8期35卷 294-298页

作者： Wei-Yu Zhou Zi-Han Xi Ning-Ning du Li Ye Ming-Hao Jiang Jin-Le Hao Bin Lin Guo-dong Yao Xiao-Xiao Huang Shao-Jiang Song Key Laboratory of Computational Chemistry-Based Natural Antitumor drug research&development Liaoning ProvinceEngineering Research Center of Natural Medicine Active Molecule Research&DevelopmentLiaoning ProvinceKey Laboratory of Natural Bioactive Compounds Discovery&ModificationShenyangSchool of Traditional Chinese Materia Medic1Shenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Structure-Based drug design and discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China

Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.***.1.0^(2,6).0^(8,13)]pentadecane and tetracyclo[5.***.0.1^(2,5).2^(4,11)]tridecane central frameworks were iso-lated from daphne altaica Pall.,representing two types of unparalleled meroterpenoid *** struc-tures were elucidated by extensive spectroscopic analysis,nuclear magnetic resonance(NMr)calcula-tions,dP4+analysis and electronic circular dichroism(ECd)*** plausible biosynthetic path-ways for 1 and 2 were ***,2 exerted potent neuroprotective activities which were su-perior to trolox at 12.5 and 25μmol/***,1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than *** docking simulations were performed to explore the inter-molecular interaction of compounds 1 and 2 with *** bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.

关键词： daphne altaica Pall. molecular networking MolNetEnhancer NAP Unprecedented meroterpenoid frameworks Neuroprotective activities Acetylcholinesterase inhibitors

ribonucleotide reductase M2 (rrM2): regulation, function and targeting strategy in human cancer

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Genes & diseases 2024年第1期11卷 218-233页

作者： Zanwen Zuo Zerong Zhou Yuzhou Chang Yan Liu Yuping Shen Qizhang Li Lei Zhang Innovative drug r&d center College of Life SciencesHuaibei Normal UniversityHuaibeiAnhui 235000China National"111"center for Cellular regulation and molecular Pharmaceutics Key Laboratory of Fermentation Engineering(Ministry of Education)Hubei Key Laboratory of Industrial MicrobiologyCooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province)and School of Food and Biological EngineeringHubei University of TechnologyWuhanHubei 430068China department of Biomedical Informatics The Ohio State UniversityColumbusOH 43210USA School of Agriculture and Biology and Engineering Research Center of Cell&Therapeutic AntibodyMinistry of EducationShanghai Jiao Tong UniversityShanghai 200240China College of Chemistry and Bioengineering Hunan University of Science and EngineeringYongzhouHunan425199China department of Pharmaceutical Botany School of PharmacyNaval Medical UniversityShanghai 200433China

ribonucleotide reductase M2(rrM2)is a small subunit in ribonucleotide reduc-tases,which participate in nucleotide metabolism and catalyze the conversion of nucleotides to deoxynucleotides,maintaining the dNTP pools for dNA biosynthesis,repair,and ***2 performs a critical role in the malignant biological behaviors of *** structure,regulation,and function of rrM2 and its inhibitors were ***2 gene can produce two transcripts encoding the same ***2 expression is regulated at multiple levels during the processes from transcription to ***,this gene is associated with resistance,regulated cell death,and tumor *** order to develop and design inhibitors of rrM2,appropriate strategies can be adopted based on different ***,a greater appreciation of the characteristics of rrM2 is a benefit for understanding tumorigenesis,resistance in cancer,and tumor ***,rrM2-targeted therapy will be more attention in future therapeutic approaches for enhancement of treatment effects and amelioration of the dismal prognosis.

关键词： Function Inhibition regulation resistance rrM2

Super-assembled sandwich-like Au@MSN@Ag nanomatrices for high-throughput and efficient detection of small biomolecules

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Nano research 2022年第3期15卷 2722-2733页

作者： dantong Zhao Chunxia Ma Meng Gao Yong Li Bo Yang Hui Li runhao Zhang Minglu Hao Jing Huang Kang Liang Pu Chen Lei Xie rong rong Biao Kong College of Medicine Shandong University of Traditional Chinese MedicineJinan 250355China Shandong Analysis and Test center National Supercomputer Research Center of Advanced MaterialsAdvanced Materials InstituteQilu University of Technology(Shandong Academy of Sciences)Jinan 250014China Heze Institute for Food and drug Control Heze 274000China School of Chemical engineering and Graduate School of Biomedical engineering The University of New South WalesNSW 2052Australia department of Chemical engineering University of WaterlooWaterlooOntarioN2L 3G1Canada department of Chemistry Shanghai Key Lab of Molecular Catalysis and Innovative MaterialsiChEMFudan UniversityShanghai 200032China

small biomolecules(m/z<500)are the material basis of organisms and participate in life activities,but their comprehensive and accurate detection in complex samples remains a ***-assisted laser desorption/ionization ma... 详细信息

small biomolecules(m/zre the material basis of organisms and participate in life activities,but their comprehensive and accurate detection in complex samples remains a ***-assisted laser desorption/ionization mass spectrometry(MALdI-MS)is a powerful detection tool for molecular analysis with high *** development of a new matrix is essential to improve the efficiency of the MALdI-MS for molecular compound *** this work,the sandwich-like gold nanoparticles@mesoporous silica nanocomposite@silver nanoparticles(Au@MSN@Ag)nanospheres were prepared by layer-by-layer super-assembly strategy,and can be used as a novel matrix for the quantitative detection and enrichment of small biomolecules by *** sandwich-like nanospheres form a unique plasma resonant cavity that effectively absorbs the laser energy,while the homogeneous mesoporous structure of MSN can lock the analyte,which is essential for efficient LdI of small *** to traditional matrices,Au@MSN@Ag shows the advantages of low background,wide application range,high sensitivity,super high salt and protein tolerance,and good *** example,the detection limit of glucose was as low as 5 fmol,and showed a good linear relationship in the range of 1−750μg/***@MSN@Ag assisted LdI-MS allows the enrichment and detection of small molecules in traditional Chinese medicine(TCM)without derivatization and purification,classification of herbs using the accurate quantitative results oligosaccharides,and identification of gelatin by amino acid *** research could help in designing more efficient nanostructure matrices and further explored the application of LdI-MS.

关键词： matrix-assisted laser desorption/ionization mass spectrometry(MALdI-MS) matrix sandwich-like nanostructures small biomolecules traditional Chinese medicine(TCM)

Characterization of a small-molecule inhibitor targeting NEMO/IKKβto suppress colorectal cancer growth

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Signal Transduction and targeted Therapy 2022年第4期7卷 1219-1231页

作者： Zhenlong Yu Jian Gao Xiaolei Zhang Yulin Peng Wenlong Wei Jianrong Xu Zhenwei Li Chao Wang Meirong Zhou Xiangge Tian Lei Feng Xiaokui Huo Min Liu Mingliang Ye de-an Guo Xiaochi Ma Pharmaceutical research center Second Affiliated HospitalDalian Medical UniversityDalian 116000China College of Pharmacy College(Institute)of Integrative MedicineDalian Medical UniversityDalian 116044China Jiangsu Key Laboratory of New drug research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Shanghai research center for Modernization of Traditional Chinese Medicine National Engineering Research Center for TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Academy of Integrative Medicine Shanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China Neurology department Dalian University Affiliated Xinhua HospitalDalian 116021China

NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic ***,using a combined strategy of molecular pharmacological phenotyping,proteomics and bioinformatics analysis,Shikonin(SHK)is identified as a potential inhibitor of the IKKβ/NEMO *** destabilizes IKKβ/NEMO complex with IC_(50) of 174 nM,thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in *** addition,we also elucidated the potential target sites of SHK in the NEMO/IKKβ*** study provides some new insights for the development of potent small-molecule PPI inhibitors.

关键词： IKKβ colorectal cancer

Efficient electrochemical reduction of CO to C_(2) products on the transition metal and boron co-doped black phosphorene

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Chinese Chemical Letters 2022年第4期33卷 2183-2187页

作者： Lingyi Kong Zhe Chen Qinghai Cai Lichang Yin Jingxiang Zhao College of Chemistry and Chemical engineering and Key Laboratory of Photonic and Electronic Bandgap MaterialsMinistry of EducationHarbin Normal UniversityHarbin 150025China center of Artificial Photosynthesis for Solar Fuels School of ScienceWestlake UniversityHangzhou 310024China Heilongjiang province Collaborative Innovation center of Cold region Ecological Safety Harbin 150025China Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China department of Physics and Electronic Information Huaibei Normal UniversityHuaibei 235000China

The synthesis of high-value multi-carbon products through the electrochemical reduction of carbon monoxide(COEr) is one of the promising avenues for carbon utilization and energy storage,in which searching for efficient electrocatalysts that exhibit moderate CO intermediate binding strength and low kinetic barrier for C-C coupling is a key ***,by means of comprehensive density functional theory(dFT) computations,we theoretically designed three synergistic coupling catalysts by co-doping transition metal(TM=Fe,Co and Ni) and boron(B) into the two-dimensional black phosphorene(BP),namely TMB@BP for COEr to C_(2) *** computations and ab initio molecular dynamics simulations reveal the good stability and high feasibility of these proposed TM-B@BP catalysts for practical applications and future experimental *** interestingly,high-value ethylene(C_(2)H_(4)),ethane(C_(2)H_(6)) and ethanol(C_(2)H_(5)OH) products can be obtained on these three designed electrocatalysts with ultra-small limiting potentials(-0.20~-0.41 V) and low kinetic energy barriers of C-C coupling(0.52~0.91 eV).Meanwhile,the competitive one-carbon(C_(1)) products and hydrogen evolution reaction can also be effectively *** promising activity and selectivity of these three designed electrocatalysts render them ideal candidates for CO electroreduction,thus providing a cost-effective opportunity to achieve a sustainable production of high value C_(2) chemicals and fuels.

关键词： CO reduction Electrocatalysis Multi-carbon products density functional theory 2d black phosphorene

2-APQC,a small-molecule activator of Sirtuin-3(SIrT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

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Signal Transduction and targeted Therapy 2024年第6期9卷 2748-2764页

作者： Fu Peng Minru Liao Wenke Jin Wei Liu Zixiang Li Zhichao Fan Ling Zou Siwei Chen Lingjuan Zhu Qian Zhao Gu Zhan Liang Ouyang Cheng Peng Bo Han Jin Zhang Leilei Fu West China School of Pharmacy and department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan engineering research center for Biomimetic Synthesis of Natural drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Southwestern Chinese Medicine resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Sirtuin 3(SIrT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAd^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP *** evidence has recently revealed that SIrT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation ***,discovery of SIrT3 activators and elucidating their underlying mechanisms of HF should be urgently ***,we identified a new small-molecule activator of SIrT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat ***,in SIrT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIrT3 for its protective ***,2-APQC was found to inhibit the mammalian target of rapamycin(mTOr)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial *** upon rNA-seq analyses,we demonstrated that SIrT3-pyrroline-5-carboxylate reductase 1(PYCr1)axis was closely assoiated with *** activating PYCr1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(rOS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative ***,activation of SIrT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced ***,our results demonstrate that 2-APQC is a targeted SIrT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

关键词： SIrT3 homeostasis metabolism

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

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Chinese Medical Journal 2024年第2期137卷 209-221页

作者： Shi Qiu Yaqi Qiu Linghui deng Ling Nie Liming Ge Xiaonan Zheng di Jin Kun Jin Xianghong Zhou Xingyang Su Boyu Cai Jiakun Li Xiang Tu Lina Gong Liangren Liu Zhenhua Liu Yige Bao Jianzhong Ai Tianhai Lin Lu Yang Qiang Wei department of Urology Institute of UrologyNational Clinical Research Center for Geriatrics and Center of Biomedical Big DataWest China Hospital of Sichuan UniversityChengduSichuan 610041China department of molecular Oncology Institute of Oncology Research(IOR)Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland department of Science and drug Technology University of TurinTurinItaly National Clinical research center of Geriatrics The Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610000China department of Pathology West China HospitalSichuan UniversityChengduSichuan 610041China department of Pharmaceutics and Bioengineering School of Chemical EngineeringSichuan UniversityChengduSichuan 610000China

Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment *** date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer ***,the existence of soft tumor cells in bladder tumors remains ***,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer ***:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3d Matrigel culture system was to maintain the softness of tumor *** patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOr)were determined by Western *** immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TrIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor ***:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer *** importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor ***,we demonstrated that the biomechanical stimuli arising from 3d Matrigel activated the F-actin/ITGB8/TrIM59/AKT/mTOr/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor ***,we detected a remarkable up-regulation in ITGB8,TrIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent ***:The ITGB8/TrIM59/AKT/mTOr/glycolysis axis plays a crucial role in modulating tumor softness and ***,the soft tumor cells become more sensitive to chemother

关键词： Soft tumor cells 3d Matrigel Stemness Non-muscle invasive bladder neoplasms Microfluidic analytical techniques

repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions

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Acta Pharmaceutica Sinica B 2022年第2期12卷 532-557页

作者： Leilei Fu Wenke Jin Jiahui Zhang Lingjuan Zhu Jia Lu Yongqi Zhen Lan Zhang Liang Ouyang Bo Liu Haiyang Yu Sichuan engineering research center for Biomimetic Synthesis of Natural drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Biotherapy and Cancer center West China HospitalSichuan UniversityChengdu 610041China College of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110064China State Key Laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved *** non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy,with potentially lower overall costs and shorter *** non-oncology drugs approved by FdA have been recently reported to treat different types of human cancers,with the aid of some new emerging technologies,such as omics sequencing and artificial intelligence to overcome the bottleneck of drug ***,in this review,we focus on summarizing the therapeutic potential of non-oncology drugs,including cardiovascular drugs,microbiological drugs,small-molecule antibiotics,anti-viral drugs,anti-inflammatory drugs,antineurodegenerative drugs,antipsychotic drugs,antidepressants,and other drugs in human *** also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer *** together,these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

关键词： drug repurposing Non-oncology drug Cancer therapy Cardiovascular drug Microbiological drug small-molecule antibiotics Anti-viral drug Anti-inflammatory drug