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检索条件"任意字段=第11届世界华人药物化学研讨会（ISCMC 2018）"

共 417 条记录，以下是101-110 订阅

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Discovery of cell-permeable O-GlcNAc transferase inhibitors via tethering in situ click chemistry

Discovery of cell-permeable O-GlcNAc transferase inhibitors ...

引用

第11届世界华人药物化学研讨会（iscmc 2018）

作者： Yue Wang State Key Laboratory of Natural and Biomimetic Drugs Peking University

O-GlcNAc transferase（OGT） is a key enzyme involved in dynamic O-GlcNAcylation of nuclear and cytoplasmic proteins similar to *** of cell-permeable OGT inhibitors is significant to clarify the function and regulatory mechanism of *** will establish the foundation for the development of therapeutic drugs for relevant diseases. Here,we report two cell-permeable OGT inhibitors（APNT and APBT）,developed from low-activity precursors(IC > 1 mM) via "tethering in situ click chemistry（TISCC）".Both of them were able to inhibit O-GlcNAcylation in cells without significant effects on cell viability（Figure 1）.Unusual noncompetitive inhibition of OGT was helpful to discover novel inhibitors and explore the regulatory mechanism of *** development of these molecules validates that TISCC can be utilized to discover novel lead compounds from components which exhibited very weak binding to the target.

关键词： O-GlcNAc O-GlcNAc transferase enzyme inhibitors in situ click chemistry target-guided synthesis

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The asymmetric total synthesis of sesquiterpenoids (-)-curcumenol and (-)-isocurcumenol

The asymmetric total synthesis of sesquiterpenoids (-)-curcu...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Xiangwei Meng Jing Zhou Xiaoqiang Xie Xingxian Zhang College of Pharmaceutical Sciences Zhejiang University of Technology

Curcuma Zedoaria Roscoe is a traditional Chinese medicinal herb known as "e zhu",which is a sesquiterpenoid *** 1 and isocurcumenol 2 was isolated from the essential oil of Curcuma wenyujin which is currently used as a clinical remedy for uterus cancer in *** cell culture experiments and vitro tests curcumenol 1 and isocurcumenol 2 have demonstrated that it exhibit significant cancer-tumor activity and cytocoxicity against several cancer *** to its intriguing architecture and promising biological activities,such these sesquiterpenoids have been attracting considerable attentions of organic chemists over the *** we wish to report the first asymmetric total synthesis of curcumenol 1 and isocurcumenol 2 as the typical kind of these *** retrosynthetic strategy was outlined in the following *** oxatricyclic ketone 3 was envisioned as the key intermediate,which was furnished by intramolecular cascade cycloaddition of diazoketone 3 catalyzed by Rhodium *** the compound 3 in hand,the asymmetric total synthesis of curcumenol 1 and isocurcumenol 2 is ongoing in our lab.

关键词： Guaiane sesquiterpenoid (-)-isocurcumenol (-)-curcumenol asymmetric total synthesis

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Synthesis and evaluation of ursolic acid derivatives as novel HIF-1α inhibitors

Synthesis and evaluation of ursolic acid derivatives as nove...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者：吴杰张志宏金学军朴虎日 Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain Affiliated Ministry of Education Yanbian University College of Pharmacy

HIF-1α is a transcription factor that regulates angiogenesis,invasion,metastasis,glucose uptake,and cell survival during cancer development. Ursolic acid（UA） is a pentacyclic triterpenoid found in most plant species,the positive biological effects of UA have been reported for anti-cancer and anti-inflammatory activity. In this paper,we developed novel ursolic acid derivatives aimed to develop more potent anti-cancer *** series of ursolic acid derivatives were thus designed,synthesized and evaluated for their anti-tumor *** of the synthesized compounds displayed appreciable anti-tumor *** 3 b showed the most potent activity by inhibiting the expression of HIF-1α(IC= 1.7 μM).Furthermore,MTT assay indicated that compound 3 b did not show any significant cytotoxic activity against tested cell lines.

关键词： ursolic acid anti-tumor cytotoxic HIF-1α

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Efficient syntheses of alpha-and beta-C-nucleosides and the origin of anomeric selectivity

Efficient syntheses of alpha-and beta-C-nucleosides and the ...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Tongchao Liu Zhengdan Zhu Peng Wei Dongmei Zhao Maosheng Cheng Jingkang Shen Weiliang Zhu Bing Xiong Yuelei Chen Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education Shenyang Pharmaceutical University State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences

C-Nucleosides constitute a valuable class of compounds in biological and medicinal chemistry studies. We report herein a new and efficient syntheseis of both alpha-and beta-C-nucleosides with high anomeric selectivity from N-Boc protected purine analogues（Scheme 1）.The synthetic approach features carefully designed lithiation and silane reduction *** anomeric stereochemistry outcome is dictated by the protecting group of sugar *** studies suggest that previously neglected interactions between partially positively-charged silane and the substitutions on sugar moiety play important roles in the anomeric selectivity of silane-mediated C-nucleoside synthesis.

关键词： C-Nucleosides anomeric selectivity N6-Boc protected purine analogues

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Synthesis,chemical characterization and preliminarily drugability studied on the calcium complex of enrofloxacin

Synthesis,chemical characterization and preliminarily drugab...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Mengxin Yu Houtian Yan Qizhen Yang Yancheng Liu Hong Liang State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry & Pharmaceutical SciencesGuangxi Normal University

The third-generation fluoroquinolone-type veterinary drug,enrofloxacin,was selected as bioactive Iigand to afford a coordinated complex,in which the central cation was chosen to be Ca（Ⅱ）.The metal complex of enrofloxacin was synthesized via solution method,whose structure[Ca（L）（HO）].HO was characterized by means of IR,UV,ESI-MS,elemental analysis diffraction *** antibacterial activity of the Calcium complex comparing with enrofloxacin on five clinical common bacteria（Staphylococcus aureus,Escherichia coli,Pseudomonas aeruginosa,Typhoidal salmonellosis,Proteusbacillus vulgaris） was screened by in vitro bacteriostatic *** results of the experiments indicated that the enrofloxacin and its metal complex showed different inhibition and killing effects against the tested *** inhibition activity of metal（Ca） complex was better than enrofloxacin towards Escherichia coli,and was equivalent to the free enrofloxacin ligand to the other four bacterias.

关键词： enrofloxacin Calcium complex antibacterial activity

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Design,synthesis,and structure-activity relationship of novel pan HDAC inhibitors based on indole

Design,synthesis,and structure-activity relationship of nove...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Zhangxu He Chen Liu Yi Ying Wang Liying Ma Hongmin Liu Collaborative Innovation Center of New Drug Research and Safty Evaluation Henan Provinceschoolof Pharmaceutical SciencesZhengzhou University

Histone deacetylases（HDACs） are being increasingly used as targets for chemotherapeutic intervention in *** removes an acetyl group,resulting in a compact chromatin state and thereby silencing gene *** approvals of HDAC inhibitors for the treatment of T-cell lymphoma and multiple myeloma（Figure 1）.HDAC inhibitors reported are commonly associated with dose-limiting *** design better HDACi's,it is essential to understand the structural regions necessary for *** triad of cap/linker/zinc-binding group（ZBG） is typically found in all potent HDACi's,such as *** cap region interacts with the rim of the enzyme,whereas the linker enters the deep hydrophobic tunnel to properly position the ZBG in the catalytic *** have found that HDAC is highly expressed in MGC803 cells,designed a series of derivatives containing indole that have been shown to have potent inhibitory activity.

关键词： HDACs ZBG MGC803 cells Indole

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Discovery of new tetrahydroisoquinoline-based LSD1/KDM1A inhibitors from natural product Higenamine

Discovery of new tetrahydroisoquinoline-based LSD1/KDM1A inh...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Kai Tang Bin Yu Hongmin Liu School of Pharmaceutical Sciences Zhengzhou University

In recent years,lysine specific demethylase 1 has been identified to play an vital role in epigenetic regulation of gene activation and *** products（NPs） have long been recognized as rich sources for identifying new therapeutic agents,Some NPs have been reported to be able to inhibit LSDl,such as curcumin,luteolin,myricetin and quercetin showed certain inhibition toward *** is first characterized as tetrahydroisoquinoline-based natural LSDl inhibitor with an IC value of 1.47±0.06 μM,so we further designed and synthesized multiple series of tetrahydroisoquinoline derivatives and evaluated their inhibitory activity against *** compounds showed favorable inhibitory activities with IC values ranging from 200 nM to 4 *** findings could provide new structure skeletons for the design of new potent and selective LSD1 inhibitors for disease treatment.

关键词： Natural products LSD1 inhibitors Higenamine Tetrahydroisoquinoline

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Discovery of 8-hydroxyquinoline derivatives as matrix metalloproteinase-2(MMP-2) inhibitors that inhibits proliferation and induces apoptosis

Discovery of 8-hydroxyquinoline derivatives as matrix metall...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Chen Chen Xinying Yang Hao Fang Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong University

8-Hydroxyquinolines are heterocyclic compounds characterized by various biological *** was reported that 8-Hydroxyquinoline fragments substituted at either the 5-or7-positions gave potent hits against MMP-2,with IC values in the low micromolar ***,a series of 8-Hydroxyquinoline derivatives were designed and synthesized as MMP-2 inhibitors and evaluated for their anti-proliferative *** compounds 3 and14 have stronger enzyme or cancer cell lines inhibitory effect than positive drug ***,flow cytometry analysis showed that compound 3 and 14 can promote K562 cell apoptosis in vitro after 48 h.

关键词： 8-Hydroxyquinolines MMP-2 apoptosis

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Induction of cell apoptosis and cell cycle arrest against HepG2 by two platinum complexes

Induction of cell apoptosis and cell cycle arrest against He...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Yulan Li Yancheng Liu Zhenfeng Chen Hong Liang State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and PharmacyGuangxi Normal University

Six cell lines were treated with 8-hydroxyquinoline platinum complex（complex 1） and5-chlorine-8-hydroxyquinoline platinum complex（complex 2）,respectively,which previously was reported for their antiproliferative activity and interaction with *** 2 displayed lowest IC values among them,about 5.34-19.06 μM.1 and 2 triggered cell cycle arrest at S phase on HepG2 cells at 5 μM,the increase population were 15.29%and 23.01%,*** of them significantly induced cell apoptosis,the total apoptotic were52.29%and 70.89%,*** particular concern is that the antitumor activity of 2 was more efficient than that of 1,maybe owning to 2 with one chlorine,presented a Halogen effect.

关键词： platinum complex antitumor activity cell cycle cell apoptosis

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Chiral ruthenium(Ⅱ) complexes as potential inhibitor against the growth of heptitic cancer via antiangiogenesis and DNA damage

Chiral ruthenium(Ⅱ) complexes as potential inhibitor agains...

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第11届世界华人药物化学研讨会（iscmc 2018）

作者： Gengnan Yu Jieqiong Cao Yumei Li Qiong Wu Bowen Lian Wenjie Mei School of Pharmacy Guangdong Pharmaceutical University School of Chemistry Jinan University School of Public Health Guangdong Pharmaceutical University

Ruthenium complexes have long been demeonstrated as anticancer *** a chiral ruthenium complex have been prepared and the evaluation of in vivo inhibitory activities against tumor in mice revealed that ruthenium complex can inhibit the growth of hepatitic *** antiangiogenesis result demonstrated that ruthenium complex can inhibit the growth of new vessels and show great antiangiogenesis activity to tumor with low *** TUNEL analysis comet assays and DNA binding behaviour study shown that ruthenium complex could bind to double stranded-DNA and cause the DNA damage to induce the apoptosis of tumor cells. Taken together,these results suggested that ruthenium complex have potential application as anticancer and antiangiogenesis chemical drugs with a low toxicity.

关键词： ruthenium complex anticancer antiangiogenesis DNA damage low toxicity

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