检索结果-南通市图书馆

DNA G-Quadruplexes as Targets for natural product Drug Discovery

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Engineering 2024年第7期38卷 39-51页

作者： Kai-Bo Wang Yingying Wang Jonathan Dickerhoff Danzhou Yang Borch Department of medicinal chemistry and Molecular Pharmacology College of PharmacyPurdue UniversityWest LafayetteIN 47907USA Purdue Center for Cancer research Purdue UniversityWest LafayetteIN 47907USA Department of chemistry Purdue UniversityWest LafayetteIN 47907USA Purdue Institute for Drug Discovery Purdue UniversityWest LafayetteIN 47907USA Jiangsu Key Laboratory of Bioactive natural product research&State Key Laboratory of natural Medicines China Pharmaceutical UniversityNanjing 210009China

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA *** structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer ***,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and *** products have long been an important source of drug discovery,particularly in the fields of cancer and infectious *** progress has recently been made in the discovery of naturally occurring DNA G4-targeting *** DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many ***,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from *** also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

关键词： G-quadruplex natural products Alkaloids Cancer Promoter

Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第5期14卷 2039-2056页

作者： Pei Yu Yubao Han Lulu Meng Yanyuan Tian Zhiwei Jin Jun Luo Chao Han Wenjun Xu Lingyi Kong Chao Zhang State Key Laboratory of natural Medicines Jiangsu Key Laboratory of Bioactive Natural Product ResearchSchool of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metastases,severely impacting patient survival *** vesicles,particularly exosomes,play a pivotal role in the formation and progression of osteosarcoma-related pulmonary ***,the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure,with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely *** study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor *** transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate(MARCKS)*** this phenomenon,in this study we employ cationic bovine serum albumin(CBSA)to form nanoparticles(CBSA-anta-194/215)via electrostatic interaction with antagomir-miR-194/*** nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles(anta-194/215@Exo)targeting osteosarcoma lung metastatic *** with bioengineered exosome mimetics(anta-194/215@Exo)not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing *** findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS,making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

关键词： Lung–bone transmission miR-194/215 cluster Exosome Lung metastasis Epithelial–mesenchymal transition Vasculogenic mimicry Bioengineered exosome mimetics Osteosarcoma

Progress in approved drugs from natural product resources

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of natural Medicines 2024年第3期22卷 195-211页

作者： LUO Zhongwen YIN Fucheng WANG Xiaobing KONG Lingyi State Key Laboratory of natural Medicines and Jiangsu Key Laboratory of Bioactive natural product research School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

natural products (NPs) have consistently played a pivotal role in pharmaceutical research, exerting profound impactson the treatment of human diseases. A significant proportion of approved molecular entity drugs are either directly derived from NPs orindirectly through modifications of NPs. This review presents an overview of NP drugs recently approved in China, the United States,and other countries, spanning various disease categories, including cancers, cardiovascular and cerebrovascular diseases, centralnervous system disorders, and infectious diseases. The article provides a succinct introduction to the origin, activity, development process, approval details, and mechanism of action of these NP drugs.

关键词： New drugs natural products Structural modification

Steroidal scaffold decorations in Solanum alkaloid biosynthesis

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Molecular Plant 2024年第8期17卷 1236-1254页

作者： Rosalind Lucier Mohamed O.Kamileen Yoko Nakamura Sofia Serediuk Ranjit Barbole Jens Wurlitzer Maritta Kunert Sarah Heinicke Sarah E.O'Connor Prashant D.Sonawane Department of natural product Biosynthesis Max Planck Institute for Chemical Ecology07745 JenaGermany research group Biosynthesis and NMR Max Planck Institute for Chemical Ecology07745 JenaGermany Biochemical Sciences Division CSIR-National Chemical LaboratoryPune 411008MaharashtraIndia

Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and *** it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic *** these,α-solasonine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory ***,α-solasonine andα-solamargine,along with the core steroidal aglycone solasodine,are the most widespread SGAs produced among the Solanum ***,it is still unknown how plants synthesize these bioactive steroidal *** comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from *** that converts the starting cholesterol precursorto solasodine aglycone,and the downstreamα-solasonine,α-solamargine,and malonyl-solamargine SGA *** further identified six enzymes from cultivated eggplant that catalyze the production ofα-solasonine,α-solamargine,and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation *** work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.

关键词： steroidal glycoalkaloids Solanum biosynthetic pathway α-solamargine malonyl-solamargine specialized metabolites

Paeoniflorin alleviates depression by inhibiting the activation of NLRP3 inflammasome via promoting mitochondrial autophagy

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of natural Medicines 2024年第6期22卷 515-529页

作者： SU Lili GUO Pengli GUO Xiangjuan HE Zhongmei ZHAO Yan ZONG Ying LI Jianming CHEN Weijia DU Rui College of Chinese medicinal Materials Jilin Agricultural UniversityChangchun 130118China Jilin Provincial Engineering research Center for Efficient Breeding and product Development of Sika Deer Changchun 130118China Key Laboratory of Animal production and product Quality and Security Ministry of EducationMinistry of National EducationChangchun 130118China

Depression ranks among the most common neuropsychiatric disorders *** studies examining the roles of inflammation and mitochondrial autophagy in the antidepressant efficacy of paeoniflorin(PF)are *** study aimed to elucidate PF’s antidepressant mechanism by promoting autophagy and inhibiting NLRP3 inflammasome activation using chronic unpredictable mild stimulation(CUMS)-induced C57BL/6 mouse models in vivo and corticosterone(CORT)-induced HT22 cell models in *** demonstrated that PF enhanced the viability of HT22 cells following CORT exposure,restored mitochondrial membrane poten-tial(MMP),reduced reactive oxygen species accumulation,increased LC3 fluorescence intensity,and suppressed inflammatory cy-tokine secretion and inflammation ***,PF ameliorated depressive behaviors induced by CUMS and improved damage in hippocampal *** also reduced the expression of NLRP3,ASC,Caspase-1,IL-1β,and the assembly of the NLRP3 ***,PF upregulated the expression of autophagy-related proteins in the hippocampus,facilitating the clearance of damaged mitochondria and enhancing *** role of autophagy in PF’s antidepressant effects was further confirmed through the use of the autophagy inhibitor 3-methyladenine(3-MA),which reduced the efficacy of *** conclusion,PF effectively improved depressive behaviors in CUMS-induced mice and reduced NLRP3-mediated inflammation both in vivo and in vitro,likely via the in-duction of autophagy.

关键词： Paeoniflorin Depression Autophagy NLRP3 inflammasome

Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第2期14卷 869-880页

作者： Yucheng Zhao Yuedong He Liangliang Han Libo Zhang Yuanzheng Xia Fucheng Yin Xiaobing Wang Deqing Zhao Sheng Xu Fei Qiao Yibei Xiao Lingyi Kong Department of Resources Science of Traditional Chinese Medicines School of Traditional Chinese Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China College of Bioscience and Biotechnology Hunan Agricultural UniversityChangsha 410128China Jiangsu Key Laboratory of Bioactive natural product research and State Key Laboratory of natural Medicines Department of Natural Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Crop Gene Resources and Germplasm Enhancement in Southern China Ministry of AgricultureTropical Crops Genetic Resources InstituteChinese Academy of Tropical Agricultural SciencesHaikou 517317China Institute of Botany Jiangsu Province and Chinese Academy of SciencesNanjing 210014China Department of Pharmacology School of Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Pyran-and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans,respectively,exhibiting diverse physiological and medical ***,the biosynthetic mechanisms for their core structures remain poorly *** we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in *** included three distinct *** prenyltransferases(PpPT1e3)responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors,and two novel CYP450 cyclases(PpDC and PpOC)crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran *** analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring *** possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific *** identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic *** study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

关键词： Tetrahydropyrans Tetrahydrofurans Baldwin rules Coumarins CYP450cyclase

Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 215-224页

作者： Justus Thomas Obiajulu Sievers Anom Bowolaksono R.Tedjo Sasmono Graduate School of Biology Department of BiologyFaculty of Mathematics and Natural SciencesUniversitas IndonesiaDepok 16424Indonesia Eijkman research Center for Molecular Biology National Research and Innovation AgencyCibinong 16911Indonesia Cellular and Molecular Mechanisms in Biological System research group Department of BiologyFaculty of Mathematics and Natural SciencesUniversitas IndonesiaDepok 16424Indonesia

Objective:To characterize the infection patterns and growth characteristics of the Zika virus(ZIKV)strain JMB-185 from Indonesia in various mammalian cell ***:ZIKV was grown in human(A549,HEK293,HepG2,Huh7,Jurkat,and THP-1)and non-human mammalian(RAW264.7,Vero,and Vero76)cell *** replication kinetics were measured using plaque assay,while intra-and extracellular viral RNA concentrations were assessed using *** cytometry was used to quantify the infected cells and cell viability was measured using an MTT *** ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining ***:This ZIKV strain preferentially infected the lung,kidney,and liver cell lines A549,HEK293,Huh7,Vero,and Vero76,but not the immune cells Jurkat,RAW264.7,and *** contrast,the ZIKV showed no sign of infection in HepG2 cells,while maintaining viral titer over 3 days post-infection,with no infection recorded in immunostaining,no increase in viral RNA,and no indication of cell ***:The Indonesian ZIKV strain has a similar infection profile as other strains,except for its poor infectivity on HepG2 *** on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

关键词： Zika virus Infectivity Replication Cell lines In vitro

Synthesis of Anti-Pancreatic Cancer natural product Majusculamide D and Analogues Reveals a Preliminary Structure-Activity Relationships

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of chemistry 2024年第6期42卷 605-610页

作者： Xiuhe Zhao Mengxue Lv Xiaonan Xi Yaxin Lu Liang Wang Yue Chen The State Key Laboratory of medicinal Chemical Biology College of PharmacyNankai UniversityTianjin300350 China College of chemistry Nankai UniversityTianjin300071 China

The total synthesis of majusculamide D(1)was achieved from commercially available *** addition,we synthesized eight analogues including three stereoisomers of majusculamide D that differ in the fatty acid *** analogues including a simplified analogue 29 exhibited significant nanomolar-level IC50 values against Panc-1 cells in MTT assays.A preliminary SAR analysis indicated that the hydroxyl group at C10 and C2−C3 unsaturated double bond of majusculamide D were essential in maintaining the high activity against Panc-1 cells and the orientation of C40-Me and C42-Me groups was tolerable.

关键词： Majusculamide D natural products SAR Anti-pancreatic cancer Lipopentapeptide

Morroniside from Corni Fructus ameliorates type 2 diabetes in mice by regulating intestinal microbiota dysbiosis

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Food Science and Human Wellness 2024年

作者： Xueqi Tang Yilin Bai Yinxia Wu Yue Yang Xiaobo Yu Jing Chen Xiaochang Xue Jiefang Kang National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China The Key Laboratory of medicinal Resources and natural Pharmaceutical chemistry， The Ministry of Education College of Life Sciences， Shaanxi Normal University

As one of the most common metabolic diseases， type 2 diabetes (T2D) has become a public health concern with rising global prevalence. Corni fructus (CF)， a traditional Chinese herb utilized for centuries as homologous medicinal and food resources， has been widely used to treat glucose and lipid metabolism disorders. However， as a core active ingredient of CF， whether and how morroniside (MOR) improves T2D is still unclear. This study aimed to explore the pathways by which MOR ameliorates T2D in mice induced by high-fat diet (HFD) and low-dose streptozotocin (STZ) through 16S rRNA gene sequencing. We found that MOR treatment significantly ameliorated body weight loss， hyperglycemia， hyperlipidemia and insulin resistance in T2D mice. In addition， MOR remarkably improved inflammation- and oxidative stress-driven hepatic and pancreatic injuries in the model mice. Mechanistically， MOR rehabilitated the dysregulated diversity and constitution of the gut microbiota in T2D mice， with significant changes in relative abundance in genus such as Lactobacillus， Lachnospiraceae＿NK4A136＿group， and Lachnospiraceae＿UCG-006 which are believed to be highly correlated with serum parameters and insulin resistance in mice with T2D. Therefore， we infer that MOR improves T2D at least partially by maintaining the host microbiota homeostasis， and MOR may be a promising candidate for T2D treatment.

关键词：