作者： Chen, Kexin;Yao, Xu;Tang, Ting;Chen, Li-Mei;Xiao, Can;...

期刊： Medicinal Chemistry Research,2021年30(3):519-534 ISSN：1054-2523

通讯作者： Liu, Yi;Zheng, Xing;Jiang, Zhong-Xing

作者机构： [Liu, Yi; Zheng, Xing; Tang, Ting; Chen, Hong-Fei; Chen, Li-Mei; Wang, Jing-Yi; Yao, Xu; Chen, Kexin; Xiao, Can] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Grp Lead Compound,Dept Pharm,Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Zhong-Xing; Chen, Kexin] Wuhan Univ, Sch Pharmaceut Sci, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Wuhan 430071, Hubei, Peoples R China.

通讯机构： [Liu, Y; Zheng, X] U;[Jiang, Zhong-Xing] W;Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Grp Lead Compound,Dept Pharm,Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.;Wuhan Univ, Sch Pharmaceut Sci, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Wuhan 430071, Hubei, Peoples R China.

关键词： Diabetes;PTP1B;Insulin resistance;Thiazoles;Thiazolidines

摘要： As a disease closely related to the metabolic syndrome, diabetes has become a public health issue that severely affects many people’s quality of life. The search for novel anti-diabetic agents remains the cornerstone to control this challenging disease. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin and leptin signaling pathways, has turned out to be a potential target of type II diabetes mellitus (T2DM) and obesity. In recent years, the development of novel anti-diabetic drugs based on PTP1B inhibitors has captured the attention of many researchers. Thiazole, a five-membered heterocycle containing sulfur and nitrogen atoms, has been considered as an essential core skeleton for various active compounds. Furthermore, thiazolidines, representing a series of compounds with saturated thiazole rings, widely exist in natural products and synthetic compounds with a variety of pharmacological activities. Here, we focus on the emphasis of PTP1B in diabetes and the development of PTP1B inhibitors based on thiazole and thiazolidine derivatives in the past decade. Many PTP1B inhibitors and their chemical structures, selectivity, potency, and structure-activity relationship have been elaborated. The great majority of PTP1B inhibitors containing thiazole and thiazolidine moieties described in this review exhibit preferable activities, which would be of importance for the rational design and efficient application of PTP1B inhibitors with anti-diabetes activity. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

语种： 英文

作者： Wu, Tingjuan;Yao, Xu;Wang, Guan;Liu, Xiaohe;Chen, Hongfei;...

期刊： LETTERS IN DRUG DESIGN & DISCOVERY,2020年17(9):1084-1101 ISSN：1570-1808

通讯作者： Zheng, Xing

作者机构： [Wang, Guan; Yang, Zehua; Chen, Hongfei; Yao, Xu; Wu, Tingjuan; Liu, Xiaohe; Zheng, Xing] Univ South China, Dept Pharm, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Wu, Tingjuan; Zheng, Xing] Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang, Peoples R China.;[Wang, Guan] Hangzhou Med Coll, Dept Publ Hlth, Hangzhou, Peoples R China.

通讯机构： [Zheng, Xing] U;Univ South China, Dept Pharm, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.

关键词： bardoxolone;nonsteroid antiinflammatory agent;oleanolic acid;oleanolic acid derivative;sulforhodamine B;triterpenoid;ursolic acid;antidiabetic activity;antiinflammatory activity;antimicrobial activity;antineoplastic activity;antiosteoporotic activity;antioxidant activity;antiviral activity;biological activity;diabetes mellitus;drug activity;drug design;drug effect;drug mechanism;drug structure;drug synthesis;EM-2 cell line;hepatic stellate cell;human;IC50;inflammation;liver function;malignant neoplasm;medicinal plant;nonhuman;osteoclastogenesis;osteoporosis;priority journal;Review;structure activity relation

摘要： Background: Oleanolic Acid (OA) is a ubiquitous product of triterpenoid compounds. Due to its inexpensive availability, unique bioactivities, pharmacological effects and non-toxic properties, OA has attracted tremendous interest in the field of drug design and synthesis. Further-more, many OA derivatives have been developed for ameliorating the poor water solubility and bio-availability. Objective: Over the past few decades, various modifications of the OA framework structure have led to the observation of enhancement in bioactivity. Herein, we focused on the synthesis and medicinal performance of OA derivatives modified on A-ring. Moreover, we clarified the relationship between structures and activities of OA derivatives with different functional groups in A-ring. The future application of OA in the field of drug design and development also was discussed and inferred. Conclusion: This review concluded the novel achievements that could add paramount information to the further study of OA-based drugs. © 2020 Bentham Science Publishers.

语种： 英文

作者： Wu, Tingjuan;Chen, Kexin;He, Shuangyan;Liu, Xiaohe;Zheng, Xing*;...

期刊： Organic Process Research & Development,2020年24(8):1364-1372 ISSN：1083-6160

通讯作者： Zheng, Xing;Jiang, Zhong-Xing

作者机构： [Wu, Tingjuan; Chen, Kexin; He, Shuangyan; Liu, Xiaohe; Zheng, Xing] Univ South China, Dept Pharm, Grp Lead Compound, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Zhong-Xing; Wu, Tingjuan; Chen, Kexin] Wuhan Univ, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Sch Pharmaceut Sci, Wuhan 430071, Peoples R China.

通讯机构： [Zheng, Xing] U;[Jiang, Zhong-Xing] W;Univ South China, Dept Pharm, Grp Lead Compound, Hengyang 421001, Hunan, Peoples R China.;Wuhan Univ, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Sch Pharmaceut Sci, Wuhan 430071, Peoples R China.

关键词： Aliphatic compounds;Biochemistry;Ethylene glycol;Medical applications;Physicochemical properties;Polyols;Biomedical applications;Camptothecin (CPT);Drug development;Efficient synthesis;Gold standards;Rational design;Synthetic strategies;Therapeutic efficacy;Polyethylene glycols

摘要： Poly(ethylene glycol)s (PEGs) are the most used polymers in biomedicine, and their so-called “stealth” effects are the “gold standard” for biomaterials. However, the polydispersity in regular PEGs hampers their biomedical application, especially in modification of small molecular drugs (SMDs). To address this issue, many synthetic strategies for monodisperse PEGs (M-PEGs) have recently been developed. More importantly, M-PEGs have been successfully employed to modify SMDs, and the crucial roles of M-PEGs in PEGylated SMDs have been discovered in many cases. Herein we summarize the strategies for the synthesis of M-PEGylated SMDs, including Movantik, NKTR-181, polidocanol, propofol, and camptothecin, and the important roles of M-PEGs in optimizing the physicochemical properties, bioavailability, and therapeutic efficacy of SMDs. M-PEGylation is a convenient and effective strategy to develop novel SMDs, especially on the basis of marketed drugs. This review may shed light on the rational design and efficient synthesis of new M-PEGylated SMDs.

语种： 英文

作者： Li, Yaling;Liu, Maojun;Song, Xiong;Zheng, Xia;Yi, Jiali;...

期刊： Frontiers in Pharmacology,2020年11:563341 ISSN：1663-9812

通讯作者： Yang, Jun;Chu, Chun

作者机构： [Liu, Maojun; Liu, Da; Wang, Sen; Yang, Jun; Song, Xiong; Li, Yaling; Yi, Jiali; Zheng, Xia] Univ South China, Affiliated Hosp 1, Dept Cardiol, Hengyang, Peoples R China.;[Chu, Chun] Univ South China, Affiliated Hosp 2, Dept Pharm, Hengyang, Peoples R China.

通讯机构： [Yang, Jun; Chu, Chun] U;Univ South China, Affiliated Hosp 1, Dept Cardiol, Hengyang, Peoples R China.;Univ South China, Affiliated Hosp 2, Dept Pharm, Hengyang, Peoples R China.

关键词： autophagy;cell aging;hydrogen sulfide;myocardial fibrosis;Sirt6/AMPK pathway

摘要： Stress aging of myocardial cells participates in the mechanism of myocardial fibrosis (MF). Previous studies have shown that hydrogen sulfide (H2S) can improve MF, however the specific internal mechanism remains still unclear. Therefore, this study aims to explore whether H2S can improve myocardial cell aging induced by high glucose and myocardial fibrosis in diabetic rats by activating autophagy through SIRT6/AMPK. We observed that HG (high glucose, 33 mM) induced down-regulation of endogenous H2S-producing enzyme CSE protein expression, increased cell senescence, down-regulation of autophagy-related proteins Beclin1, Atg5, Atg12, Atg16L1, and inhibition of SIRT6/AMPK signaling pathway in H9c2 cardiomyocytes. H2S (NaHS: 400 μM) could up-regulate CSE protein expression, inhibit cell senescence, activate autophagy and SIRT6/AMPK signaling pathway. On the contrary, no above phenomena was achieved upon addition of CSE inhibitor PAG (dl-propargylglycine: mmol/L). In order to further elucidate the relationship between H2S and SIRT6/AMPK signaling pathway, dorsomorphin dihydrochloride (Dor), an inhibitor of AMPK signaling pathway, was added to observe the reversal of H2S’s inhibitory effect on myocardial cell aging. At the same, streptozotocin (STZ; 40 mg/kg) was injected intraperitoneally to build an animal model of diabetic SD rats. The results showed that myocardial collagen fibers were significantly deposited, myocardial tissue senescent cells were significantly increased and the expression of CSE protein was down-regulated, while SIRT6/AMPK signaling pathway and cell autophagy were significantly inhibited. H2S-treated (NaHS; 56 μmol/kg) could significantly reverse the above phenomenon. In conclusion, these findings suggest that exogenous H2S can inhibit myocardial cell senescence and improve diabetic myocardial fibrosis by activating CSE and autophagy through SIRT6/AMPK signaling pathway. © Copyright © 2020 Li, Liu, Song, Zheng, Yi, Liu, Wang, Chu and Yang.

语种： 英文

作者： Wang, Xuemeng;Li, Yu;Wu, Tingjuan;Yang, Zhigang;Zheng, Xing;...

期刊： Biomacromolecules,2020年21(2):725-731 ISSN：1525-7797

通讯作者： Zhou, Xin;Jiang, Zhong-Xing

作者机构： [Jiang, Zhong-Xing; Wang, Xuemeng; Yang, Zhigang] Wuhan Univ, Wuhan, Peoples R China.;[Li, Yu; Zhou, Xin; Chen, Shizhen] Chinese Acad Sci, Wuhan, Peoples R China.;[Wu, Tingjuan; Zheng, Xing] Univ South China, Hengyang, Peoples R China.

通讯机构： [Zhou, Xin] C;[Jiang, Zhong-Xing] W;Chinese Acad Sci, Wuhan, Peoples R China.;Wuhan Univ, Wuhan, Peoples R China.

摘要： In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it is challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation strategies, including backbone PEGylation, side-chain PEGylation, and highly branched PEGylation, have been developed. In a comparative fashion, the impact of PEGylation strategies and monodisperse PEG sizes on the physicochemical and biological properties, including lipophilicity, thermosensitivity, biocompatibility, plasma stability, and drug delivery capability, of peptidic polymers has been quantitatively studied. It was found that the physicochemical and biological properties of PEGylated peptidic polymers can be quantitatively fine-tuned and accurately predicted through these monodisperse PEGylation strategies. After the comparative study, a side-chain monodisperse PEGylated peptidic polymer was chosen as fluorine-19 magnetic resonance and fluorescence dual-imaging traceable drug delivery vehicle. Our study may not only promote the transformation of PEGylation from an empirical technology to a quantitative science but also shed light on the rational design of PEGylated biomaterials and pharmaceutics.

语种： 英文

作者： Xiang, Yijun;Ge, Qianyi;Wu, Shulei;Zheng, Xing*;Yang, Zehua*

期刊： RSC Advances,2020年10(16):9563-9578 ISSN：2046-2069

通讯作者： Zheng, Xing;Yang, Zehua

作者机构： [Ge, Qianyi; Xiang, Yijun; Yang, Zehua; Zheng, Xing; Yang, ZH; Wu, Shulei] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Zheng, X; Yang, ZH] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.

摘要： P-stereogenic pincer-metal complexes are one of the most interesting pincer type organometallic compounds. Many kinds of this type of complexes were synthesized and used as catalysts in asymmetric catalysis. On the basis of our work in this field, this paper reports the recent progress in P-stereogenic pincer chemistry, including the synthesis of P-stereogenic pincer ligands, the synthesis of P-stereogenic pincer-metal complexes, and the achievements in P-stereogenic pincer-metal complex catalyzed asymmetric synthesis. This journal is © The Royal Society of Chemistry.

语种： 英文

作者： Zhu, Junfei;Zhang, Huaibin;Chen, Kexin;Li, Yu;Yang, Zhigang;...

期刊： Advanced Healthcare Materials,2020年9(3):e1901331 ISSN：2192-2640

通讯作者： Jiang, Zhong-Xing

作者机构： [Jiang, Zhong-Xing; Zhu, Junfei; Zhang, Huaibin; Yang, Zhigang] Wuhan Univ, Sch Pharmaceut Sci, Res Ctr Fluorinated Pharmaceut, Hubei Prov Engn & Technol, Wuhan 430071, Hubei, Peoples R China.;[Li, Yu; Zhou, Xin; Chen, Shizhen; Zhang, Huaibin] Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan, Wuhan 430071, Hubei, Peoples R China.;[Chen, Kexin; Zheng, Xing] Univ South China, Grp Lead Compound, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.

通讯机构： [Jiang, Zhong-Xing] W;Wuhan Univ, Sch Pharmaceut Sci, Res Ctr Fluorinated Pharmaceut, Hubei Prov Engn & Technol, Wuhan 430071, Hubei, Peoples R China.

关键词： drug delivery;imaging;liposome;polyethylene glycols;stimuli-responsive biomaterials

摘要： Monodisperse polyethylene glycols-modified (M-PEGylated) biomaterials exhibit high structural accuracy, biocompatibility, and fine-tunable physicochemical properties. To develop "smart" drug delivery systems in a controllable and convenient manner, a peptidic M-PEG "comb" with fluorinated L-lysine side chains and a fluorescent N-terminal is conveniently prepared as a (19) F magnetic resonance imaging ((19) F MRI) and fluorescence dual-imaging traceable and thermo-responsive "add-on" module for liposomal theranostics in cancer therapy. The peptidic M-PEG "comb" has high biocompatibility, thermo-responsivity with a sharp lower critical solution temperature, an aggregation-induced emission fluorescence, and high (19) F MRI sensitivity. As a highly branched amphiphile, it self-assembles and firmly anchors on the doxorubicin-loaded liposomal nanoparticles, which M-PEGylates the liposomes and facilitates the thermo-responsive drug release and drug tracking with dual-imaging technologies. In a rodent xenograft model of human liver cancer HepG2 cells, the M-PEGylated liposomes exhibit long in vivo half time, low toxicity, high tumor accumulation, "hot spot" (19) F MRI, and therapeutic efficacy. With accurately programmable chemical structure, fine-tunable physicochemical and biological properties to meet the demands of diagnosis, drug delivery, and therapy, the M-PEG "comb" is promising as a versatile "add-on" module for rapid and convenient formulation of various "smart" theranostics.

语种： 英文

作者： Li, Yaling;Liu, Maojun;Yi, Jiali;Song, Xiong;Zheng, Xia;...

期刊： 生物化学与生物物理学报(英文),2020年52(12):1325-1336 ISSN：1672-9145

通讯作者： Yang, Jun;Chu, Chun

作者机构： [Liu, Maojun; Liu, Da; Wang, Sen; Yang, Jun; Song, Xiong; Li, Yaling; Yi, Jiali; Zheng, Xia] Univ South China, Dept Cardiol, Affiliated Hosp 1, Hengyang 421001, Peoples R China.;[Chu, Chun] Univ South China, Dept Pharm, Affiliated Hosp 2, Hengyang 421001, Peoples R China.

通讯机构： [Yang, Jun; Chu, Chun] U;Univ South China, Dept Cardiol, Affiliated Hosp 1, Hengyang 421001, Peoples R China.;Univ South China, Dept Pharm, Affiliated Hosp 2, Hengyang 421001, Peoples R China.

关键词： acute myocardial infarction;apoptosis;endoplasmic reticulum stress–autophagy axis;hydrogen sulfide;myocardial reconstruction

摘要： During acute myocardial infarction, endoplasmic reticulum (ER) stress-induced autophagy and apoptosis have been shown as important pathogeneses of myocardial reconstruction. Importantly, hydrogen sulfide (H2S), as a third endogenous gas signaling molecule, exerts strong cytoprotective effect on anti-ER stress, autophagy regulation and antiapoptosis. Here, we showed that H2S treatment inhibits apoptosis by regulating ER stress-autophagy axis and improves myocardial reconstruction after acute myocardial infarction. We found that H2S intervention improved left ventricle function, reduced glycogen deposition in myocardial tissue mesenchyme, and inhibited apoptosis. Moreover, the expressions of fibrosis indicators (Col3a1 and Col1a2), ER stress-related proteins (CHOP and BIP/ERP78), autophagy-related proteins (Beclin and ATG5), apoptosis protein (Bax), as well as fibrosis protein Col4a3bp were all decreased after treatment with H2S. H2S administration also maintained MMP/TIMP balance. Mechanistically, H2S activated the PI3K/AKT signaling pathway. In addition, H2S treatment also reduced the expressions of ER stress-related proteins, autophagy-related proteins, and apoptins in in vitro experiments. Interestingly, activation of ER stress-autophagy axis could reverse the inhibitory effect of H2S on myocardial apoptosis. Altogether, these results suggested that exogenous H2S suppresses myocardial apoptosis by blocking ER stress-autophagy axis, which in turn reverses cardiac remodeling after myocardial infarction. © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

语种： 英文

作者： Yang, Mei-Fang;Yao, Xu;Chen, Li-Mei;Gu, Jin-Ying;Yang, Ze-Hua;...

期刊： Archiv der Pharmazie,2020年353(7):2000044- ISSN：0365-6233

通讯作者： Zheng, Zi-Tong

作者机构： [Yang, Ze-Hua; Chen, Hong-Fei; Chen, Li-Mei; Yao, Xu; Yang, Mei-Fang; Zheng, Zi-Tong; Gu, Jin-Ying; Zheng, Xing] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol,Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Zheng, Zi-Tong] U;Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol,Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.

关键词： biological activity;breast cancer;resveratrol derivatives;structure-activity relationship;synthesis

摘要： <jats:title>Abstract</jats:title><jats:p>Resveratrol is a natural phytoestrogen produced by plants to protect themselves from injury, UV irradiation, and fungal attack. The main active structure is <jats:italic>E</jats:italic>‐resveratrol, which has many pharmacological activities. As the structure of resveratrol is similar to the natural estrogen 17β‐estradiol and the synthetic estrogen <jats:italic>E</jats:italic>‐diethylstilbestrol, resveratrol is used in reducing the incidence of breast cancer. However, the therapeutic application of resveratrol is limited due to its low bioavailability. To improve its bioavailability and pharmacological activity, some resveratrol derivatives have been designed and synthesized by substitutions of methoxy, hydroxyl, and other functional groups or heterocyclic esterification either on the “A” or “B” ring, and double bonds were replaced by imine bonds and isometric heterocycles such as naphthyl and imidazole, or synthetic resveratrol oligomers. The structures, synthetic routes, and evaluation of the biological activities of these compounds are discussed. These are aimed at providing some references for the study of resveratrol derivatives in anti‐breast cancer treatment.</jats:p>

语种： 英文

作者： Liu, Renbo;Deng, Xiangping;Peng, Yijiao;Feng, Wanshi;Xiong, Runde;...

期刊： Bioorganic Chemistry,2020年96:103652 ISSN：0045-2068

通讯作者： Tang, Guotao

作者机构： [Deng, Xiangping; Xie, Zhizhong; Liu, Renbo; Lei, Xiaoyong; Peng, Yijiao; Zou, Yang; Tang, Guotao; Feng, Wanshi; Xiong, Runde; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang City, Peoples R China.;[Deng, Xiangping; Liu, Renbo; Tang, Guotao] Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang City, Hunan, Peoples R China.;[Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Tang, Guotao] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.

关键词： Anti-tumor;Flavonoid;Glycolysis;HIF-1alpha;Microtubules

摘要： 5,6,7-Trimethoxy flavonoid salicylate derivatives were designed by the joining of three important pharmacophores (TMP, flavonoid, and SA) according to the combination principle. A series of novel trimethoxy flavonoid salicylate derivatives were synthesized and their in vitro anti-tumor activities were evaluated. Among these derivatives, compound 7f exhibited excellent antiproliferative activity against HGC-27 cells and MGC-803 cells with IC50 values of 10.26 ± 6.94 μM and 17.17 ± 3.03 μM, respectively. Subsequently, the effects on cell colony formation (clonogenic survival assay), cell migration (wound healing assay), cell cycle distribution (PI staining assay), cell apoptosis (Hoechst 33258 staining assay and annexin V-FITC/PI dual staining assay), lactate level (lactate measurement), microtubules disarrangement (immunofluorescence staining analysis) and docking posture (molecular docking simulation) were determined. Further western blot analysis confirmed that compound 7f could effectively down-regulate the expression of glycolysis-related proteins HIF-1α, PFKM and PKM2 and tumor angiogenesis-related proteins VEGF. Overall, these studies suggested that compound 7f, as the representative compound of those, might be a promising candidate for the treatment of gastric cancer and deserved the further studies. © 2020 Elsevier Inc.

语种： 英文

作者： Yang, Zhi-Fang;Xu, Chang;Zheng, Xing*;Zhang, Xingang*

期刊： Chemical Communications,2020年56(17):2642-2645 ISSN：1359-7345

通讯作者： Zheng, Xing;Zhang, Xingang

作者机构： [Yang, Zhi-Fang; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Xu, Chang; Zhang, Xingang] Univ Chinese Acad Sci, Key Lab Organofluorine Chem, Ctr Excellence Mol Synth, Shanghai Inst Organ Chem,Chinese Acad Sci, 345 Lingling Lu, Shanghai 200032, Peoples R China.

通讯机构： [Zheng, Xing; Zhang, Xingang] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;Univ Chinese Acad Sci, Key Lab Organofluorine Chem, Ctr Excellence Mol Synth, Shanghai Inst Organ Chem,Chinese Acad Sci, 345 Lingling Lu, Shanghai 200032, Peoples R China.

摘要： A nickel-catalyzed tandem reaction of N-vinylamides with arylboronic acids and bromodifluoroacetate has been developed. The use of amide carbonyl as a chelating group efficiently furnishes a series of protected alpha,alpha-difluoro-gamma-amino acid esters. The reaction can also extend to bromoacetate and 2-bromomalonate. The advantages of this protocol are high functional group tolerance and a broad substrate scope, including a variety of N-vinylamides. In particular, the use of removable amide carbonyl groups provides potential opportunities for applications in peptide chemistry and protein engineering.

语种： 英文

作者： Xiao, Xuan;Yao, Xu;Yu, Jiao;Tang, Ting;Xiao, Can;...

期刊： Journal of Fluorine Chemistry,2020年240:109649 ISSN：0022-1139

通讯作者： Zheng, Xing;Lin, Jin-Hong;Xiao, Ji-Chang

作者机构： [Gu, Jinying; Tang, Ting; Xiao, Xuan; Yao, Xu; Xiao, Can; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Dept Pharm,Grp Lead Compound, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Hunan, Peoples R China.;[Yu, Jiao; Xiao, Xuan; Lin, Jin-Hong; Xiao, Can; Lin, JH; Xiao, Ji-Chang] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.

通讯机构： [Zheng, Xing; Lin, JH; Xiao, JC] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Dept Pharm,Grp Lead Compound, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Hunan, Peoples R China.;Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.

关键词： gem-Difluoroolefins;Alcohols;Phosphonium ylide;Difluorocarbene;One-step synthesis

摘要： The development of efficient protocols for the synthesis of gem-difluoroolefins has received increasing attention. Given the ubiquity of hydroxyl group in biologically active molecules and synthetic intermediates, we developed a one-step protocol for the conversions of alcohols into gem-difluoroolefins. The reactions of alcohols with Ph3P+CF2CO2−/Burgess reagent in DMSO occurred smoothly to afford the final products in moderate to high yields. DMSO is not only necessary for the oxidation process, but also important for the stabilization of phosphonium ylide by trapping difluorocarbene. © 2020 Elsevier B.V.

语种： 英文

作者： Luo, Xingrui;Pailla, Santhosh Kumar;Gao, Fei;Zheng, Xing*;Wang, Ruowen*

期刊： Tetrahedron,2020年76(9):130926 ISSN：0040-4020

通讯作者： Zheng, Xing;Wang, Ruowen

作者机构： [Luo, Xingrui; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Pailla, Santhosh Kumar; Wang, Ruowen; Luo, Xingrui; Gao, Fei] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Inst Mol Med,State Key Lab Oncogenes & Related Ge, Shanghai 00240, Peoples R China.;[Wang, Ruowen; Luo, Xingrui] Tsinghua Univ, Dept Biotechnol & Biomed, Yangtze Delta Reg Inst, Jiaxing 314006, Zhejiang, Peoples R China.

通讯机构： [Zheng, Xing] U;[Wang, Ruowen] S;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Inst Mol Med,State Key Lab Oncogenes & Related Ge, Shanghai 00240, Peoples R China.

关键词： Amino acids;Prodrug;SuFEx;Fluorosulfate

摘要： Sulfur (VI) Fluoride Exchange (SuFEx) chemistry is proposed as a new generation of click chemistry with potential in drug discovery and biological study. Herein we report a simple and convenient approach to synthesize amino acid derivatives functionalized with aryl fluorosulfonyl group from a simple building block. Promoted by 1,1'-Carbonyldiimidazole (CDI), methyl protected amino acids and other amines were efficiently functionalized with SO2F by the reaction with 4-((fluorosulfonyl)oxy)benzoic acid giving fluorosulfonylated amides (FSAs) as products. We also demonstrated that FSAs are useful building blocks in drug discovery. The conjugation of FSA with pharmaceutical phenols by SuFEx efficiently introduced amino acid moiety into target molecule, providing a series of prodrugs with diverse property. (C) 2020 Elsevier Ltd. All rights reserved.

语种： 英文

作者： Deng, Tao;Mao, Xianglan;Xiao, Yan;Yang, Zhigang;Zheng, Xing;...

期刊： Bioorganic & Medicinal Chemistry Letters,2019年29(4):581-584 ISSN：0960-894X

通讯作者： Jiang, Zhong-Xing

作者机构： [Deng, Tao; Mao, Xianglan; Jiang, Zhong-Xing; Yang, Zhigang] Wuhan Univ, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Wuhan 430071, Hubei, Peoples R China.;[Deng, Tao; Mao, Xianglan; Jiang, Zhong-Xing; Yang, Zhigang] Wuhan Univ, Sch Pharmaceut Sci, Wuhan 430071, Hubei, Peoples R China.;[Xiao, Yan; Jiang, Zhong-Xing; Zheng, Xing] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.

通讯机构： [Jiang, Zhong-Xing] W;Wuhan Univ, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Wuhan 430071, Hubei, Peoples R China.;Wuhan Univ, Sch Pharmaceut Sci, Wuhan 430071, Hubei, Peoples R China.

关键词： Anticancer drugs;Camptophecin;Polyethylene glycols;Prodrug;SN38

摘要： Camptothecin, which represents a class of natural products with high anticancer activity, suffers low water solubility which hampers its clinic application. To address this issue, monodisperse polyethylene glycols were employed to modify this class of natural products, including Camptothecin, 10-Hydroxycamptothecin, and SN38. Through selective modification with a series of monodisperse polyethylene glycols, 31 Camptothecin derivatives, including 9 ethers and 22 carbonates, were prepared using a macrocyclic sulfate-based strategy with high efficacy. Monodisperse polyethylene glycols modification provided the Camptothecin derivatives with high purity and fine-tunable water solubility. Through the physicochemical and biological assays, a few novel prodrugs with good solubility, cytotoxicity, and valuable drug release profile were identified as promising anticancer drug candidates.

语种： 英文

作者： Li, Yang;Li, Yan-peng;He, Jun*;Liu, Ding;Zhang, Qi-zhi;...

期刊： MINI-REVIEWS IN MEDICINAL CHEMISTRY,2019年19(7):555-568 ISSN：1389-5575

通讯作者： He, Jun;Liu, Yunmei

作者机构： [Liu, Yunmei; Li, Kang; Guo, Yu; Liu, Ding; Li, Yan-peng; Tang, Guo-Tao; Zhang, Qi-zhi; Li, Yang; Zheng, Xing] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[He, Jun] Univ South China, Inst Chem & Chem Engn, Hengyang 421001, Peoples R China.;[He, J; Liu, YM] Univ South China, Inst Pharm & Pharmacol, 28 Changshcng West Rd, Hengyang 421001, Peoples R China.

通讯机构： [He, J; Liu, YM] U;Univ South China, Inst Pharm & Pharmacol, 28 Changshcng West Rd, Hengyang 421001, Peoples R China.

关键词： 5 [(4 fluorobenzyl)oxy] 7 hydroxy 2 phenyl 4h chromen 4 one;7 o (ethoxycarbonyl)alkyl chrysin;7 o (ethoxycarbonyl)alkylamino chrysin;antiinfective agent;antivirus agent;chrysin;chrysin derivative;selenium;unclassified drug;antineoplastic agent;biological product;chrysin;flavonoid;antidiabetic activity;antineoplastic activity;antiviral activity;apoptosis;Article;cancer cell destruction;chemical modification;clinical outcome;drug mechanism;drug research;drug screening;drug structure;Enterovirus A71;G2 phase cell cycle checkpoint;gene therapy;human;inflammation;M phase cell cycle checkpoint;nonhuman;structure activity relation;animal;chemistry;drug development;drug effect;neoplasm;procedures;structure activity relation;Animals;Antineoplastic Agents;Apoptosis;Biological Products;Drug Discovery;Flavonoids;Humans;Neoplasms;Structure-Activity Relationship

摘要： Chrysin is a natural product of a flavonoid compound. Chemically, chrysin consists of two phenyl rings (A and B) and a heterocyclic ring (C). Biologically, chrysin exerts many different physiological activities. In recent years, with the in-depth development for more active drugs, the synthesis and biological activities of chrysin derivatives have been well studied. Besides, structure-activity relationship of chrysin revealed that the chemical construction meets the critical chemical structural necessities of flavonoids for numerous pharmacological activities. It is generally believed that modified chrysin could be more potent than unmodified chrysin. Different modification in the rings of chrysin could possess various degrees of biological activities. This review aims to summarize the mechanism for the activities of chrysin and its derivatives in different rings. We also explored the relationship between biological function and structure-activity of substituted chrysin derivatives with different functional groups. The influence of chrysin derivatives on the proliferation and apoptosis of cancer cells is also investigated. Development of novel drugs based on the biological functions of chrysin could better improve clinical outcomes of affected population, especially for tumor patients and diabetic patients. © 2019 Bentham Science Publishers.

语种： 英文

作者： Xiang, Meng-Hui;Qi, Qiao-Yan;Zheng, Xing*;Zhao, Xin*

期刊： Tetrahedron Letters,2019年60(26):1727-1731 ISSN：0040-4039

通讯作者： Zheng, Xing;Zhao, Xin

作者机构： [Xiang, Meng-Hui; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Zhao, Xin; Xiang, Meng-Hui; Qi, Qiao-Yan] Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Synthet & Self Assembly Chem Organ Funct, Ctr Excellence Mol Synth, 345 Lingling Rd, Shanghai 200032, Peoples R China.

通讯机构： [Zheng, Xing] U;[Zhao, Xin] C;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Synthet & Self Assembly Chem Organ Funct, Ctr Excellence Mol Synth, 345 Lingling Rd, Shanghai 200032, Peoples R China.

关键词： Self-assembly;Supramolecular polymer;Amphiphilic;pH-responsive

摘要： A novel amphiphilic supramolecular polymer (ASP) with rigid linear main chain has been constructed by the co-assembly of a rigid amphiphilic monomer and cucurbit[8]uril (CB[8]) in water, driven by CB[8]-based host-guest interactions. The ASP could further self-assemble into well-defined architectures including nanotubes and 2D films, depending on its concentration. Moreover, pH-responsive behavior of the ASP was also observed. (C) 2019 Elsevier Ltd. All rights reserved.

语种： 英文

作者： Deng, Xiangping;Li, Zhongli;Xiong, Runde;Liu, Juan;Liu, Renbo;...

期刊： Biomedicine & Pharmacotherapy,2019年109:1659-1669 ISSN：0753-3322

通讯作者： Xie, Zhizhong;Tang, Guotao

作者机构： [Li, Zhongli; Liu, Juan; Tang, Guotao; Peng, Junmei; Zheng, Xing; Deng, Xiangping; Xie, Zhizhong; Liu, Renbo; Lei, Xiaoyong; Xiong, Runde; Cao, Xuan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Chen, Yanming] Jiuzhitang Co Ltd, Changsha, Hunan, Peoples R China.;[Xie, ZZ; Tang, GT] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Xie, ZZ; Tang, GT] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.

关键词： FS-7;MGC-803;Anticancer;HIF-1 alpha;Glycolysis

摘要： In this study, we investigated the anticancer effects of FS-7, a flavonoid salicylate derivative, in human gastric carcinoma MGC-803 cell line and studied its preliminary anticancer effects. FS-7 displayed greater in vitro cytotoxicity against MGC-803 cell line compared with 5-Fu and had a certain extent of selectivity to cancer cells. The flow cytometry analysis revealed that FS-7 induced apoptosis MGC-803 cells and mainly caused cells arrest in the G2/M phase in a concentration-dependent manner. Additionally, FS-7 inhibited the colony formation and cell migration in a concentration-dependent manner. Notably, FS-7 noticeably down-regulated glycolysis-related protein HIF-1 alpha, HK-II and PFKP expression in a concentration-dependent manner, possibly causing glycolysis inhibition. Importantly, compared with 5-Fu, FS-7 showed better anticancer activity in the MGC-803 xenograft murine tumor models. Collectively, the present study provided a promising anticancer drug candidate for gastric cancer therapy.

语种： 英文

作者： 杨泽华;伍造端;陈洪飞;郑兴

期刊： 广东化工,2019年46(1):143-144 ISSN：1007-1865

作者机构： 南华大学药学院药物药理研究所;湖南省分子靶标新药研究协同创新中心;[伍造端] 南华大学附属南华医院;[陈洪飞; 郑兴; 杨泽华] 南华大学

关键词： 一流本科教育;绿色化学;药物化学实验

摘要： 创建一流本科教育是当前我国高等教育的重要方向。绿色化学是当代社会对化学学科提出的新要求,应充分应用到我国的一流本科教育当中。本文以药物化学实验教学中盐酸普鲁卡因的合成为例,针对现用教材中耗时长、收率低、能耗高的缺点,将原教材中对硝基苯甲酸与二乙胺基乙醇脱水成酯的合成路线,改进为对硝基苯甲酰氯与二乙胺基乙醇酰化成酯的路线。将原反应时间从6小时缩短到0.5小时,并提高收率,减少废物排放,降低能耗,极大方便学生实验的开展。

语种： 中文

作者： Lv, Yuncheng;Yang, Jing;Gao, Anbo;Sun, Sha;Zheng, Xilong;...

期刊： 生物化学与生物物理学报(英文),2019年51(5):471-483 ISSN：1672-9145

通讯作者： Peng, Tianhong;Zhong, Liyuan;Zhao, Guojun

作者机构： [Chen, Xi; Sun, Sha; Lv, Yuncheng; Wan, Wei; Gao, Anbo; Xie, Wei; Peng, Tianhong; Guo, Dongming; Zhong, Liyuan; Li, Suyun; Peng, TH] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;[Yang, Jing] Univ South China, Affiliated Hosp 1, Clin Med Res Inst, Hengyang 421001, Peoples R China.;[Zheng, Xilong] Univ Calgary, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol, Hlth Sci Ctr, Calgary T2N 4N1, AB, Canada.;[Tang, Chaoke] Univ South China, Inst Cardiovasc Res, Med Res Ctr, Hengyang 421001, Peoples R China.;[Zhao, Guojun] Guilin Med Univ, Dept Histol & Embryol, Guilin 541004, Peoples R China.

通讯机构： [Peng, TH; Zhong, LY] U;[Zhao, Guojun] G;Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;Guilin Med Univ, Dept Histol & Embryol, Guilin 541004, Peoples R China.

关键词： sortilin;ABCA1;macrophage;cholesterol efflux;atherosclerosis

摘要： Sortilin is closely associated with hyperlipidemia and the risk of atherosclerosis (AS). The role of sortilin and the underlying mechanism in peripheral macrophage are not fully understood. In this study, we investigated the effect of macrophage sortilin on ATP-binding cassette transporter A1 (ABCA1) expression, ABCA1-mediated cholesterol efflux, and aortic AS. Macrophage sortilin expression was upregulated by oxidized low-density lipoproteins (ox-LDLs) in both concentrationand time-dependent manners. Its expression reached the peak level when cells were incubated with 50 ?g/ml ox-LDL for 24 h. Overexpression of sortilin in macrophage reduced cholesterol efflux, leading to an increase in intracellular total cholesterol, free cholesterol, and cholesterol ester. Sortilinwas found to bind with ABCA1 protein and suppress macrophage ABCA1 expression, resulting in a decrease in cholesterol efflux from macrophages. The inhibitory effect of sortilin in cholesterol efflux was partially reversed by treatment with chloroquine, a lysosomal inhibitor. On the contrary, the ABCA1 protein level and ABCA1-mediated cholesterol efflux is increased by sortilin short hairpin RNA transfection. The fecal and biliary cholesterol 3H-sterol from cholesterolladen mouse peritoneal macrophage was reduced by sortilin overexpression through lentivirus vector (LV)-sortilin in low-density lipoprotein receptor knockout mice, which was prevented by cotreatment with chloroquine. Treatment with LV-sortilin reduced plasma high-density lipoprotein and increased plasma ox-LDL levels. Accordingly, aortic lipid deposition and plaque area were exacerbated, and ABCA1 expression was reduced in mice in response to infection with LVsortilin alone. These effects of LV-sortilin were partially reversed by chloroquine. Sortilin enhances lysosomal degradation of ABCA1 protein and suppresses ABCA1-mediated cholesterol efflux from macrophages, leading to foam cell formation and AS development. © 2019 The Author(s) .

语种： 英文

作者： Long, Jin;Chen, Jia;Li, Rong;Liu, Zhuo;Xiao, Xuan;...

期刊： SYNLETT,2019年30(2):181-184 ISSN：0936-5214

通讯作者： Zheng, Xing;Lin, Jin-Hong;Xiao, Ji-Chang

作者机构： [Long, Jin; Li, Rong; Xiao, Xuan; Liu, Zhuo; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Long, Jin; Xiao, Xuan; Lin, Jin-Hong; Chen, Jia; Xiao, Ji-Chang; Liu, Zhuo; Lin, JH] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China.

通讯机构： [Zheng, Xing; Lin, JH; Xiao, JC] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China.

关键词： epoxide;dichlorination;dibromination;1,2-dihalides;triphenylphosphine

摘要： Ph 3 P/I - -promoted dichlorination and dibromination of epoxides by using XCH 2 CH 2 X (X = Cl or Br) as the halogen source and reaction solvent is described. All reagents are widely available and easy to handle, and mild conditions and operational simplicity make this protocol attractive. © Georg Thieme Verlag Stuttgart - New York.

语种： 英文