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Chiral Phenol-2NO Ligand Cooperation with Achiral Organic Base in the Zn(II)-Catalyzed Asymmetric Alkylation Reaction of Indoles

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Chinese Journal of Chemistry 2024年第13期42卷 1474-1480页

作者： Ke-Lan Xu Yu-Heng Wang Xi-Rui Wang Pan Hu Bo-Wen Pan Wen-Jing Zhang Zi-Yue Chen Ying Zhou Xiong-Li Liu National&Local Joint engineering research center for the Exploitation of Homology resources of southwest Medicine and Food Guizhou UniversityGuiyangGuizhou 550025China College of pharmaceutical Sciences Guizhou University of Traditional Chinese MedicineGuiyangGuizhou 550025China Green Catalysis center and College of ChemistryZhengzhou UniversityZhengzhouHenan 450001China

The privileged C_(2)-symmetric rigid phenol-type ligand is more attractive but challenging in asymmetric ***,we designed and synthesized a class of rigid-featured chiral tridentate Phenol-2NO ligands,that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone-based N-oxide moiety,from readily available L-prolinamides in operationally simple two steps and up to 44%overall *** importantly,using an achiral quinoline derivative as an additive,the newly developed Phenol-2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II)to form a highly enantioselective catalyst for the asymmetric Michael-type Friedel-Crafts alkylation reaction of indoles with 2,*** yields(up to 90%)and high enantioselectivities(up to 99%ee)are obtained for a wide range of substrates under mild *** and DFT calculations revealed the reaction mechanism and the origins of the *** also represented the first activation of phenol-type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis.

关键词： Phenol-2NO C_(2)-Symmetric Rigid-featured Tridentate ligand Asymmetric catalysis Alkylation Synthesis design Heterocycles

A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou Guangdong Provincial Key Laboratory of New Drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for research and Evaluation of Drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Lewwin pharmaceutical research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug Druggability

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

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

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Oncology research 2024年第5期32卷 943-953页

作者： JIANBO ZHOU FENG WAN BIN XIAO XIN LI CHENG PENG FU PENG Department of Pharmacology West China School of PharmacySichuan UniversityChengduChina State Key Laboratory of southwestern Chinese Medicine resources Chengdu University of Traditional Chinese MedicineChengduChina Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologySichuan UniversityChengduChina Chengdu No.1 pharmaceutical Co. Ltd.PengzhouChina Chengdu Push bio-Technology Co. Ltd.ChengduChina

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,*** the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well *** this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent *** induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in ***,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 *** triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 *** mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

关键词： Metochalcone Breast cancer Lung cancer SASP JAK2/STAT3

Constructing osteo-inductive bio-ink for 3D printing through hybridization of gelatin with maleic acid modified bacterial cellulose by regulating addition volumes of maleic acid solution

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Journal of bioresources and bioproducts 2024年第3期9卷 336-350页

作者： Xucai Wang Dengxian Wu Wei Liao Yaxuan Liu Wenhui Pei Jixian Wang Jiayu Gu Peng Wang Kai Lan Caoxing Huang Co-Innovation center for Efficient Processing and Utilization of Forest resources College of Chemical EngineeringNanjing Forestry UniversityNanjing 210037China State Key Laboratory of pharmaceutical biotechnology Department of Sports Medicine and Adult Reconstructive SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNahanjing 210008China Children's Hospital of Nanjing Medical University Nanjing 210008China Jiangsu Institute of Metrology Nanjing 210023China Department of Forest biomaterials College of Natural ResourcesNorth Carolina State UniversityRaleigh NC 27695USA

Bacterial cellulose(BC)is an exopolysaccharide with unique properties that has been applied in various ***,the dense and intertwined nature of BC fibers limits its use in certain applications,including 3D printing scaffolds for bone *** this work,a controllable BC-based bio-ink for 3D printing was successfully prepared by modifying the neat BC through maleic acid(MA)treatment,aiming to promote bone tissue *** achieve homogeneous BC dispersions while preserving its crystalline and chemical properties,BC was modified by MA solution(60%,w/V)with solid-liquid ratio from 1꞉5 to 1꞉50(w/V)to obtain MA-BC *** analysis results from microstructure,chemical group,crystallinity,and wettability indicated that the BC/MA solution with ratio of 1꞉30 demonstrated the best pre-treatment performance to obtain ***,by combining MA-BC with gelatin,we successfully formulated MA-BC-GEL gels with favorable rheological properties and compression modulus,which can be used as promising bio-inks for 3D bioprinting *** vitro tests demonstrated 1꞉30 MA-BC possessed excellent biocompatibility,a significant ability to express the alkaline phosphatase gene and osteogenic-related genes,and facilitated the formation of mineralized *** utilization of this novel bio-ink in scaffold preparation for bone regeneration highlights the promising application of modified BC in bone tissue engineering field.

关键词： Bacterial cellulose Maleic acid Osteogenic activity Printability

Therapeutic potential and mechanism of functional oligosaccharides in inflammatory bowel disease: a review

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Food Science and Human Wellness 2023年第6期12卷 2135-2150页

作者： Xiaochun Yang Deyong Zeng Chongyang Li Wenchen Yu Guilin Xie Yingchun Zhang Weihong Lu School of Chemistry and Chemical engineering Harbin Institute of TechnologyHarbin 150001China Sichuan Gongda southwest Food research Co. Ltd.Bazhong 636063China The Intelligent Equipment research center for the Exploitation of Characteristic Food&Medicine resources Chongqing Research Institute of Harbin Institute of TechnologyChongqing 401135China

Inflammatory bowel disease(IBD)is characterized by recurrent attacks and long courses,and the number of patients has expanded rapidly year by ***,current conventional strategies exist serious adverse *** this case,it is an urgent issue to find out an effective and safe *** oligosaccharides possess safe and excellent physiological activities,and have attracted enormous attention due to their great therapeutic potential for *** review emphasizes the attenuating effects of distinct functional oligosaccharides on IBD and their structure,and summarizes the main mechanisms from the aspects of regulating intestinal fl ora structure,repairing intestinal barrier,modulating immune function and mediating related signaling pathways in order to reveal the relationship between functional oligosaccharides,immune regulation,intestinal epithelial cells,gut fl ora and IBD *** possess excellent protective effects on IBD,and can be considered as safe and functional ingredients in the health food and pharmaceutical industry.

关键词： Oligosaccharides Colitis Pathogenesis Signaling pathway Action mechanism

Cordyceps biodiversity and industrialization of Cordyceps militaris

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Cordyceps biodiversity and industrialization of Cordyceps mi...

Coleoptile Purple Line Regulated by A-P Gene System Is a Valuable Marker Trait for Seed Purity Identification in Hybrid Rice

中国菌物学会2023年学术年会

作者： Ting-Chi Wen Feng-Yao Long Yuan-Ping Xiao Ling-Sheng Zha Ji-Chuan Kang Kevin D.Hyde The engineering and research center for southwest bio-pharmaceutical resources of National Education Ministry of China Guizhou University School of Pharmacy Guizhou University center of Excellence in Fungal research Mae Fah Luang University

Cordyceps sensu lato create tremendous economic value due to their medicinal,biological and nutritional *** objective of this study is classification of Cordyceps *** optimization of large-scale production conditions for *** and ***,this study helps in industrialization of *** than 120 species of Cordyceps *** been identified from China,Thailand and Russia based on morphology and multi-gene phylogenetic *** them,30 are new to the *** militaris has been used as a common mushroom in China and the market demand for artificial *** has increased *** the industrial application works,(1) Solid-state fermentation for fruiting-body and cordycepin production:the optimization strategies in solid medium culture lead to a fruit body yield increased 67.96%(about 1.73 g/bottle) and cordycepin yield in fruiting-body increased 55.36%(0.87%).Larger particle size of rice in the medium offers better fruit body growth,and the cordycepin production prefers smaller particle size.(2)Solid-state fermentation only for cordycepin production:medium components glucose,peptone,adenine and histidine have been *** levels of variables for CCD experiments were selected according to the above results of the One-factor-at-a-time method;maximum response of 18.92 mg/g cordycepin at levels of glucose26.25 g/L,peptone 26.25 g/L,adenine 7.50 g/L,and histidine 4.50 g/L as optimized medium *** is the first report for improving the cordycepin production by using additives in this *** from colony sector mutation could be used for screening high-yield strains in cordycepin production and colony colour is one of the markers to detect fruit body and cordycepin production.(3) The separation and purification process of cordycepin:this optimization strategy leads to crystal of 60.45g with ratio of pure 98.05%,and the recovery rate is 43%.Our production line capacity is about 200kg/

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Rice science 2022年第5期29卷 451-461,I0019-I0031页

作者： DU Shuanglin WANG Zhongwei CHEN Yun TAN Yao LI Xiang ZHU Wenping HE Guanghua LEI Kairong GUO Longbiao ZHANG Yi State Key Laboratory for Conservation and Utilization of bio-resources in Yunnan/research center for Perennial Rice engineering and Technology in Yunnan/School of Agriculture Yunnan UniversityKunming 650091China biotechnology research Institute Chongqing Academy of Agricultural SciencesChongqing 401329China Key Laboratory of Application and Safety Control of Genetically Modified Crops/Rice research Institute Academy of Agricultural SciencesSouthwest UniversityChongqing 400715China State Key Laboratory of Rice biology China National Rice Research InstituteHangzhou 310006China

In plants,a large number of anthocyanin biosynthetic genes encoding enzymes and regulatory genes encoding transcription factors are required for anthocyanin *** purple lines are two purple lines on both sides of coleoptiles after seed ***,the molecular mechanism of coleoptile purple line is not clear in rice so *** this study,two major dominant genes,coleoptile purple line 1(OsCPL1,also known as OsC1)and coleoptile purple line 2(OsCPL2),were isolated via map-based cloning,and both of them were required for anthocyanin biosynthesis of coleoptile purple line in *** knockout and complementation experiments confirmed that OsC1 was required for purple color in most organs,such as coleoptile line,sheath,auricle,stigma and apiculus,whereas OsCPL2 was just required for coleoptile purple ***1 was predominantly expressed in coleoptiles,flag leaves,and green panicles,and highly expressed in young leaves,whereas OsCPL2 was predominantly expressed in coleoptiles,and extremely lowly expressed in the other tested ***-of-function of either OsC1 or OsCPL2 resulted in significant reduction of transcript levels of multiple anthocyanin biosynthesis genes in *** purple line was further used as a marker trait in hybrid *** identification in hybrid rice seeds via coleoptile purple line just needed a little water,soil and a small plate and could be completed within 5 *** marker and field identification analyses indicated that coleoptile purple line was reliable for the hybrid seed purity *** findings disclosed that coleoptile purple line in rice was regulated by two major dominant genes,OsC1 and OsCPL2,and can be used as a simple,rapid,accurate and economic marker trait for seed purity identification in hybrid rice.

关键词： OsC1 OsCPL2 coleoptile purple line anthocyanin seed purity identification marker trait

MALDI ToF Investigation of the Reaction of Soy Protein Isolate with Glutaraldehyde for Wood Adhesives

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Journal of Renewable Materials 2023年第3期11卷 1439-1450页

作者： Qianyu Zhang Antonio Pizzi Hong Lei Xuedong Xi Ming Cao Long Cao Yunnan key Laboratory of Wood Adhesives and Glue Products College of Material Science and EngineeringSouthwest Forestry UniversityKunming650224China International Joint research center for biomass Materials Southwest Forestry UniversityKunming650224China Universitéde Lorraine LERMAB-ENSTIB 27 rue Philippe SeguinEpinal88000France

Soy protein adhesives are currently a hot research topic in the wood panels industry for the abundant raw material reserves,reasonable price and outstanding environmental *** their poor water resistance,low bonding strength and intolerance to mold are major drawbacks,so that proper modification before use is *** is one of the more apt cross-linking agents for soybean protein adhesives,which can effectively improve the bonding strength and water resistance of the ***,glutaraldehyde is also an efficient and broad-spectrum fungicide that can significantly improve the anti-fungal properties of a soy protein *** the work presented here,matrix assisted laser desorption ionization(MALDI-ToF)mass spectrometry and Fourier transform infrared spectroscopy techniques were used to analyze the reaction mechanism of glutaraldehyde cross-linking soybean *** results confirmed the reaction of the aldehyde group with amino groups of the side chains and the amide groups of the peptide linkages constituting the skeletal chain of the *** laboratory plywood and particleboard bonded with glutaraldehyde-soy bean protein adhesives were prepared to determine the adhesive bonding properties,the dry strength,24 h cold water soaking wet strength and 3 h hot water(63°C)wet strength of plywood were 2.03,1.13 and 0.75 MPa,respectively,which satisfied the requirements of industrial production.

关键词： bio-based adhesives soy bean protein MALDI-ToF particleboard plywood