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β-Carboline alkaloids from the roots of Peganum harmala L.

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Chinese Journal of Natural Medicines 2024年第2期22卷 171-177页

作者： li Shengge ZHANG Qin WANG Yuetong liN Bin li dahong HUA Huiming HU Xu Henan Key Laboratory of Zhang Zhongjing Formulate and Herbs for Immunoregulation Zhang Zhongjing Traditional School of Chinese MedicineNanyang Institute of TechnologyNanyang 473004China Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala *** these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial *** 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-*** structures of these compounds were elucidated by spectroscopic data and quantum mechanical *** biosynthetic pathways of 1−3 were ***,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was ***,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),***,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).

关键词： β-Carboline alkaloids Peganum harmala Structure elucidation Cytotoxic activity

li dahong's Art World

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China's Foreign Trade 2016年第2期 58-59页

作者：李大鸿中国书画家协会中华书画艺术家协会中国华夏万里行书画家协会文化部中国山水画创作院环球华商协会书画艺委会中南海画册编委会泰山揽胜图创作委员会北京东方名家画院

Alkaloid Dimers Isolated from Thalictrum baicalense Have Antitumor Activities

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Chinese Journal of Chemistry 2022年第15期40卷 1831-1841页

作者： Jingjing Xue Yuetong Wang Fangshen liu Hangao Yang Bin lin Zhanlin li Yongkui Jing dahong li Huiming Hua Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyangLiaoning 110016China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China

Comprehensive Summary A pair of heterodimeric isoquinoline alkaloid enantiomers,(+)thaliberberine A,five new thalifaberine-type aporphine-benzylisoquinoline(ABl)alkaloids,thalicultratines M-Q,and thirteen known analogues were isolated from the roots of Thalictrum baicalense *** *** structures were determined by extensive spectroscopic methods and ECD *** A featuring a novel carbon skeleton coupled by two different classes of isoquinoline alkaloids,protoberberine and phthalidoisoquinoline,represents the first natural product with the berberine skeleton substituted at *** biosynthetic routes of 1 are proposed.

关键词： Thalictrum baicalense Heterodimeric isoquinoline alkaloid Thalifaberine-type ABI alkaloids Antitumor activity Apoptosis

Molecular glues modulate protein functions by inducing protein aggregation:A promising therapeutic strategy of small molecules for disease treatment

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维普期刊数据库

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3548-3566页

作者： Hongyu Wu Hong Yao Chen He Yilin Jia Zheying Zhu Shengtao Xu dahong li Jinyi Xu State Key Laboratory of Natural Medicines Department of Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009China Division of Molecular Therapeutics&Formulation School of Pharmacythe University of NottinghamUniversity Park CampusNottingham NG72RDUK Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationSchool of Traditional Chinese Materia MedicaShenyang Pharmaceutical UniversityShenyang 110016China

Molecular glues can specifically induce aggregation between two or more proteins to modulate biological *** recent years,molecular glues have been widely used as protein *** addition,however,molecular glues play a variety of vital roles,such as complex stabilization,interactome modulation and transporter inhibition,enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug *** most molecular glues are identified serendipitously,exploration of their systematic discovery and rational design are *** this review,representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization,homo-polymerization and hetero-dimerization according to their aggregation modes,and we attempt to elucidate their mechanisms of *** particular,we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development:starting point,optimization and identification.

关键词： Small molecule Molecular glue Dimerization Polymerization Protein–protein interaction

New possible silver lining for pancreatic cancer therapy:Hydrogen sulfide and its donors

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1148-1157页

作者： Xu Hua Yan Xiao Jianan Sun Bao Ji Shanshan Luo Bo Wu Chao Zheng Peng Wang Fanxing Xu Keguang Cheng Huiming Hua dahong li Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationSchool of Traditional Chinese Materia MedicaShenyang Pharmaceutical UniversityShenyang 110016China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Cardiovascular and Cerebrovascular Medicine Nanjing Medical UniversityNanjing 211166China Molecular Imaging Laboratory MGH/MIT/HMS Athinoula A.Martinos Center for Biomedical ImagingDepartment of RadiologyMassachusetts General Hospital/Harvard Medical SchoolCharlestownMA 02129USA PET Center Department of Radiology and Biomedical ImagingYale University School of MedicineNew HavenCT 06520USA Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 210009China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and PharmacyGuangxi Normal UniversityGuilin 541004China

As one of the most lethal diseases,pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment ***,pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been *** combinations of new drugs,multimodal therapies,and adjuvants prolong survival,most patients still relapse after surgery and eventually ***,the search for more effective treatments for pancreatic cancer is highly relevant and *** a newly re-discovered mediator of gasotransmission,hydrogen sulfide(H2S)undertakes essential functions,encompassing various signaling complexes that occupy key processes in human *** evidence indicates that H2S exhibits bimodal modulation of cancer ***,endogenous or low levels of exogenous H2S are thought to promote cancer,whereas high doses of exogenous H2S suppress tumor ***,inhibition of endogenous H2S production also suppresses tumor ***,H2S biosynthesis inhibitors and H2S supplementation(H2S donors)are two distinct strategies for the treatment of ***,modulation of endogenous H2S on pancreatic cancer has not been studied so ***,H2S donors and their derivatives have been extensively studied as potential therapeutic agents for pancreatic cancer therapy by inhibiting cell proliferation,inducing apoptosis,arresting cell cycle,and suppressing invasion and migration through exploiting multiple signaling *** far as we know,there is no review of the effects of H2S donors on pancreatic *** on these concerns,the therapeutic effects of some H2S donors and NO-H2S dual donors on pancreatic cancer were summarized in this *** H2S donors may be promising compounds for pancreatic cancer treatment.

关键词： Pancreatic cancer Hydrogen sulfide donor Sulfur-containing compound Cell proliferation Antitumor effect Signaling pathway

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2905-2922页

作者： Peilu Song Fan Zhao dahong li Jiqiang Qu Miao Yao Yuan Su Hanxun Wang Miaomiao Zhou Yujie Wang Yinli Gao Feng li Dongmei Zhao Fengjiao Zhang Yu Rao Mingyu Xia Haitao li Jian Wang Maosheng Cheng Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China MOE Key Laboratory of Protein Sciences School of Pharmaceutical SciencesMOE Key Laboratory of Bioorganic Phosphorus Chemistry Chemical BiologyTsinghua UniversityBeijing 100084China MOE Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life Sciences and School of MedicineTsinghua UniversityBeijing 100084China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China School of life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShengyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Cell Biology Key Laboratory of Cell BiologyMinistry of Public Healthand Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyang 110001China

The p21 activated kinase 4(PAK4) is serine/threonine protein kinase that is critical for cancer *** by X-ray crystallography and structure-based optimization,we report a novel subseries of C-3-substituted 6-ethynyl-1 H-indole derivatives that display high potential and specificity towards group Ⅱ *** these inhibitors,compound 55 exhibited excellent inhibitory activity and kinase selectivity,displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line *** 55 exhibited potent in vivo antitumor metastatic efficacy,with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models,*** mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition(EMT).

关键词： Anti-cancer PAK4 inhibitor Kinase selectivity Cocrystallization Lung metastasis EMT

Isolation and identification of compounds from the leaves of Garcinia paucinervis

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Isolation and identification of compounds from the leaves of...

中国化学会第十一届全国天然有机化学学术会议

作者： Cuicui Jia Tong Han dahong li Zhanlin li Huiming Hua Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education and School of Traditional Chinese Materia Medica Shenyang Pharmaceutical University

Garcinia *** to Chisiaceae family,is distributed in Yunnan and Guangxi Provinces of China,Previous chemical investigations have reported that it is a prolific source of xanthones and *** of these compounds

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cnki会议

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促进心理特征与个体职业双向选择

当代青年研究 2007年第12期 59-62页

作者：李大宏洛阳理工大学

开展大学生职业生涯指导是当前我国高校心理健康教育的必然选择:它是学校心理健康教育工作的应有之义,是大学生职业生涯规划现状诉求,有利于大学生身心健康和最优发展,有效促进心理特征与个体职业的双向选择。指导内容主要表现为:依据... 详细信息

开展大学生职业生涯指导是当前我国高校心理健康教育的必然选择:它是学校心理健康教育工作的应有之义,是大学生职业生涯规划现状诉求,有利于大学生身心健康和最优发展,有效促进心理特征与个体职业的双向选择。指导内容主要表现为:依据大学生心理发展特点开展职业生涯规划指导,积极开展职业心理咨询,科学开展职业心理测评工作,以教育发展性为指向,开展持续动态的职业心理辅导。

关键词：大学生职业生涯规划指导必要性内容选择

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基于主成分分析的我国区域创新能力评价

商业时代 2010年第35期 128-129页

作者：李大洪镇江高等专科学校发展研究室

本文在分析区域创新能力内涵的基础上,建立我国区域创新能力的评价指标体系,并运用主成分分析法,对我国省级区域创新能力进行评价分析,并提出相应的政策建议。

关键词：主成分分析法区域创新能力创新能力评价 China principal component analysis based capability 评价指标体系政策建议评价分析省级内涵基础