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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

natural products:potential therapeutic agents for atherosclerosis

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Chinese Journal of natural Medicines 2022年第11期20卷 830-845页

作者： CHENG Xiaobei ZHAO Caili JIN Zhiwei HU Jianping ZHANG Zhenzhen ZHANG Chao State Key Laboratory of natural Medicines and Jiangsu Key Laboratory of Bioactive natural Product Research School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China Institute of Veterinary Medicine Jiangsu Academy of Agricultural SciencesNanjing 210014China

Atherosclerosis(AS)is an invisible killer among cardiovascular diseases(CVD),which has seriously threatened the life of *** complex pathogenesis of AS involves multiple interrelated events and cell types,such as macrophages,endothelial cells,vascular smooth muscle cells and immune ***,the efficacy of recommended statin treatment is not *** products(NPs)have attracted increasing attention with regard to their broad structural diversity and biodiversity,which makes them a promising library in the demand for lead compounds with cardiovascular protective *** can preclude the development of AS by regulating lipid metabolism,ameliorating inflammation,stabilizing plaques,and remodeling the gut microbiota,which lays a foundation for the application of NPs in clinical therapeutics.

关键词： Atherosclerosis Cardiovascular diseases Pathogenesis Target natural products

natural products and their derivatives as G-quadruplex binding ligands

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Science China Chemistry 2013年第10期56卷 1351-1363页

作者： SHAN Chan TAN Jia-Heng OU Tian-Miao HUANG Zhi-Shu School of Pharmaceutical Sciences Sun Yat-sen University

G-quadruplexes comprise a class of secondary structures that are formed in guanine-rich sequences in eukaryotic genomes and play a crucial role in the regulation of many biological events.G-quadruplexes have become targets for anticancer drugs with high selectivity *** DNA and low cytotoxicity against normal *** products and their derivatives display polymorphism,structural complexity,and potent *** is,therefore,reasonable to seek ligands targeting G-quadruplexes from natural ***,many successful examples have been reported,showing ligands with excellent anticancer *** this review,we summarized the development of research on natural products and derivatives that target G-quadruplex structures in an effort to guide future studies.

关键词： G-quadruplex binding ligands natural products derivatives

natural products against hematological malignancies and identification of their targets

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Science China(Life Sciences) 2015年第12期58卷 1191-1201页

作者： XU Ying LIU JinBao WU YingLi GUO QingLong SUN HanDong CHEN GuoQiang Department of Pathophysiology Chemical Biology Division of Shanghai Universities E-Institutes Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education Shanghai Jiao Tong University School of Medicine Institute of Health Sciences Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences-Shanghai Jiao Tong University School of Medicine State Key Laboratory of Respiratory Disease Protein Modification and Degradation Lab Department of Pathophysiology Guangzhou Medical University State Key Laboratory of natural Medicines Jiangsu Key Laboratory of Carcinogenesis and Intervention China Pharmaceutical University State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of Botany Chinese Academy of Sciences

naturally occurring molecules derived from higher plants, animals, microorganisms and minerals play an important role in the discovery and development of novel therapeutic agents. The identification of molecular targets is of interest to elucidate the mode of action of these compounds, and it may be employed to set up target-based assays and allow structure-activity relationship studies to guide medicinal chemistry efforts toward lead optimization. In recent years, plant-derived natural compounds possessing potential anti-tumor activities have been garnering much interest and efforts are underway to identify their molecular targets. Here, we attempt to summarize the discoveries of several natural compounds with activities against hematological malignancies, such as adenanthin, oridonin, gambogic acid and wogonoside, the identification of their targets, and their modes of actions.

关键词： natural products adenanthin hematological malignancies target identification

natural products as LSD1 inhibitors for cancer therapy

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Acta Pharmaceutica Sinica B 2021年第3期11卷 621-631页

作者： Yuan Fang Chao Yang Zhiqiang Yu Xiaochuan Li Qingchun Mu Guochao Liao Bin Yu Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China International Institute for Translational Chinese MedicineGuangzhou University of Chinese MedicineGuangzhou 510006China Institute of Innovation&Application Zhejiang Ocean UniversityZhoushcm 316022China School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China The People’s Hospital of Gaozhou Gaozhou 525200China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of natural Medicines China Pharmaceutical UniversityNanjing 210009China

natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase1(LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.

关键词： Epigenetic regulation Histone demethylase natural products LSD1 inhibitors Drug discovery Cancer therapy

natural products as potent inhibitors of hypoxia-inducible factor-1α in cancer therapy

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Chinese Journal of natural Medicines 2020年第9期18卷 696-703页

作者： ZHONG Jin-Cheng LI Xiao-Bo LYU Wen-Yu YE Wen-Cai ZHANG Dong-Mei College of Pharmacy Jinan UniversinyGuangzhou 510632.China Guangdong Province Key Laboratory of Pharmacodynamic Constituents 0f Traditional Chinese Medicine and New Drugs Research Jinan UniversityGuangzhou 510632China

Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α(HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evidence has demonstrated that HIF-1α promotes tumor angiogenesis, metastasis, metabolism, and immune evasion. natural products are an important source of antitumor drugs and numerous studies have highlighted the crucial role of these agents in modulating HIF-1α. The present review describes the role of HIF-1α in tumor progression, summarizes natural products used as HIF-1α inhibitors, and discusses the potential of developing natural products as HIF-1α inhibitors for the treatment of cancer.

关键词： Hypoxia-inducible factor-1α Hypoxia Cancer natural products Anticancer treatment

natural products remodel cancer-associated fibroblasts in desmoplastic tumors

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2140-2155页

作者： Rujing Chen Leaf Huang Kaili Hu Murad Research Center for Modernized Chinese Medicine Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China Division of Pharmacoengineering and Molecular Pharmaceutics Center for Nanotechnology in Drug DeliveryEshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillNC 27599USA

Desmoplastic tumors have an abundance of stromal cells and the extracellular matrix which usually result in therapeutic *** treatment prescriptions for desmoplastic tumors are usually not sufficient to eliminate the ***,through modulating cancer-associated fibroblasts(CAFs)which are the most abundant cell type among all stromal cells,natural products have improved chemotherapies and the delivery of nanomedicines to the tumor cells,showing promising ability to improve treatment effects on desmoplastic *** this review,we discussed the latest advances in inhibiting desmoplastic tumors by modeling CAFs using natural products,highlighting the potential therapeutic abilities of natural products in targeting CAFs for cancer treatment.

关键词： natural products Desmoplastic tumors Cancer-associated fibroblasts Tumor microenvironment Extracellular matrix Traditional Chinese medicine Cancer treatment

natural products that target macrophages in treating non-alcoholic steatohepatitis

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World Journal of Gastroenterology 2020年第18期26卷 2155-2165页

作者： Chun-Lin Li Wen-Jun Zhou Guang Ji Li Zhang Institute of Digestive Diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

Nonalcoholic steatohepatitis(NASH)is the progressive subtype of non-alcoholic fatty liver disease and potentiates risks for both hepatic and metabolic *** the pathophysiology of NASH is not completely understood,recent studies have revealed that macrophage activation is a major contributing factor for the disease *** integrate the immune response and metabolic process and have become promising targets for NASH *** products are potential candidates for NASH treatment and have multifactorial underlying *** involvement in the development of steatosis and inflammation in NASH has been widely *** this review,we assess the evidence for natural products or their active ingredients in the modulation of macrophage activation,recruitment,and polarization,as well as the metabolic status of *** work may highlight the possible natural products that target macrophages as potential treatment options for NASH.

关键词： Nonalcoholic steatohepatitis Macrophages natural products Inflammation Metabolism

natural products and Derivatives Targeting at Cancer Energy Metabolism:A Potential Treatment Strategy

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Current Medical Science 2020年第2期40卷 205-217页

作者： Qi-qi WANGI Ming-xue LI Chen LI Xiao-xia GU Meng-zhu ZHENG Li-xia CHEN Hua LI Wuya College of Inovation School of Pharmaceutical EngineeringKey Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversiryShenyang 110016China Hubei Key Laboratory of natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

In the 1920s,Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal *** cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic *** on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the *** recent years,plentiful studics suggest that targeting the peculiar cancer energy metabolic pathways,including glycolysis,mitochondrial respiration,amino acid metabolism,and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential *** products (NPs)are considered as the “treasure trove of small molecules drugs” and have played an extremely remarkable role in the discovery and development of anticancer *** numerous NPs have been reported to act on cancer energy metabolism ***,a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared.

关键词： cancer energy metabolism cancer therapy natural products binding targets,inhibitors