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Synthesis of 3 or 4-Substituted Pyridine-2, 6-Dicarboxylic Acid

Chinese Chemical Letters 1999年第11期10卷 903-906页

作者： Xian Hong YIN Man Ya YANG Hua Hong SHI lian quan gu(Chemistry Department, Zhongshan University. guangzhou 510275)(Chemistry Department, guangxin University for Nationalities, Nanning 530006) Chemistry Department Zhongshan University Guangzhou 510275 China Chemistry Department Guangxin Univ. for Nationalities Nanning 530006 China

Various 4-alkoxypyridine-2, 6-dicarboxylic acids were synthesized starting from 2, 6- lutidine. Through aldol condensation and Michael addition, various 4-arylpyridine-2, 6-dicarboxylic acids were synthesized starting... 详细信息

关键词： Michael reaction 2,6-lutidine analogues substituted pyridine-2,6-dicarboxylic acids

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The Mechanism on Cyclization, Debenzylation and Oxidation of 1-[1-(Benzyloxy)-3-methylnaphthalen-4-yloxy]propan-2-one

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Chinese Chemical Letters 2006年第6期17卷 769-772页

作者： Shi liang HUANG Yi LUO Zhi Shu HUANG Xian Zhang BU Pei Qing LIU Lin MA Yue Ming LI Albert S. C. CHAN lian quan gu School of Chemistry and Chemical Engineering Sun Yat-Sen University Guangzhou 510275 School of Pharmaceutical Science Sun Yat-Sen University Guangzhou 510275 Department of Applied Bioiogy ＆ Chemical Technology The Hong Kong Polytechnic University Kowloon Hong Kong

1-[1-（Benzyloxy）-3-methylnaphthalen-4-yloxy]propan-2-one （la） took place a cyclization, debenzylation and oxidation to form 9-substitued benzo[de]chromene-7,8-dione （2a） and 5-benzyl-9-substitued benzo[de]chrome... 详细信息

关键词： Mansonone F cyclization selenium dioxide sigmatropic rearrangement.

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Design, Synthesis and Evaluation of Isoliquiritigenin Derivatives as Potential Dual Inhibitors for Alzheimer Disease

Design, Synthesis and Evaluation of Isoliquiritigenin Deriva...

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2013年中国药学大会暨第十三届中国药师周

作者： Yi-Ping Chen Zhi-Shu Huang Jun Xu lian-quan gu School of Pharmaceutical Sciences Guangxi University of Chinese Medicine School of Pharmaceutical Sciences Sun Yat-sen University

＜正＞Alzheimer’s disease （AD）, the most common form of dementia in the elderly, is a progressive neurodegenerative brain disorder. The pathology of AD includes Tau protein hyperphosphorylation, aggregated amyloid beta protein （Aβ） deposits, cholinergic system dysfunction and so on. Although many influencing factors have been found to be implicated in AD, its etiology and pathogenesis remain unclear. Based on amyloid cascade hypothesis, the aggregation of Aβ has been considered to be a crucial step in the etiology of Alzheimer’s disease. Therefore, the inhibition of amyloid plaques formation and clearance of potential neurotoxic peptide by small molecular compounds are promising strategies for the prevention and treatment of AD.

关键词： Alzheimer‘s disease Amyloid-beta self-aggregation 5-lipoxygenase dual targets isoliquiritigenin derivatives

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Protective effects of Bouchardatine against non-alcoholic steatohepatitis in mice and cell

Protective effects of Bouchardatine against non-alcoholic st...

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第十届全国化学生物学学术会议

作者： Yu-Ting Lu Yong-Rao Zhi-Shu Huang lian-quan gu School of Pharmaceutical Sciences Sun Yat-sen University

Non-alcoholic fatty liver disease（NAFLD） is the hepatic manifestation of obesity and metabolic syndrome, which encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis（NASH）. The absence of an effective pharmacological therapy for NASH is a major incentive for us to search a novel therapeutic approach. Our recent study has shown that bouchardatine, a naturally occurring β-indoloquinazoline alkaloid, is an antidiabetic drug with significant lipid-lowering effects. Therefore, this article was designed to explore the activity of Bouchardatine ameliorating NASH caused due to hepatic lipid accumulation. Steatosis was induced in Huh7 cells by supplementing oleic acid（OA） and palmitic acid（PA） which was marked by significant inflammation and accumulation of lipid droplets. We observed that Bouchardatine significantly decreased triglyceride content and the expressions of inflammatory factors such as IL-6 and TNF-α. In addition, qPCR results confirmed this compound could decrease the level of these inflammatory cytokines, resulting in induction of inflammation responses. Besides, in the aspect of animal experiments, body weight, liver weight index, ALT, AST, and TG were tested. TNF-α and IL-6 levels were detected by ELISA, mRNA and protein expression in liver tissue were determined by real time PCR and Western blot. According to the above, we found that bouchardatine effectively decreased these indexes of liver in MCD mice model. To summarize, Bouchardatine had a significant effect on inhibiting the release of inflammatory factors and the TG accumulation both in cell and animal models, suggested it may be a promising candidate for the treatment of NASH.

关键词： NASH NAFLD inflammation

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Specific Recognition of Quindoline Derivatives on Promoter G-Quadruplex and the Biological Relevance

Specific Recognition of Quindoline Derivatives on Promoter G...

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第八届全国化学生物学学术会议

作者： Tian-miao Ou Yue Wu Jia-heng Tan lian-quan gu Zhi-shu Huang School of Pharmaceutical Sciences Sun Yat-sen University

＜正＞G-quadruplexes are unique secondary structure exist in various non-coding region of human genome and exhibit important biological roles in the regulation of gene replication,transcription,and *** derivatives are a modified series of derivatives from natural product cryptolepine and showed great stabilizing ability on G-quadruplex in c-myc promoter in the previous *** I will present our

关键词： G-quadruplex oncogene promoter quindoline derivatives transcription regulation

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5-N-Methylated Quindoline Derivatives as G-Quadruplex Stabilizing Ligands and Potential Inhibitors of Telomerase

5-N-Methylated Quindoline Derivatives as G-Quadruplex Stabil...

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第五届全国化学生物学学术会议

作者： Yu-Jing Lu Tian-Miao Ou Ning Sun Jia-Heng Tan Zhi-Shu Huang~* lian-quan gu~* School of Pharmaceutical Sciences,Sun Yat-sen University,guangzhou 510275,China

＜正＞A series of 5-N-methylated quindoline derivatives were designed and synthesized to develop potent telomerase *** interaction of these compounds with human telomeric G-quadruplex DNA was investigated via PCR-stop *** compounds as inhibitors of telomerase were also examined through the utilization of modified telomerase repeat amplification

关键词： 5-N-methylated quindoline synthesis telomeric G-quadruplex DNA telomerase inhibitor

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Anti-angiogenic Potentials of Quindoline Derivatives Targeting G-quadruplex Structure in Vascular Endothelial Cell Growth Factor

Anti-angiogenic Potentials of Quindoline Derivatives Targeti...

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第五届全国化学生物学学术会议

作者： Tian-Miao Ou Yu-Jing Lu Ning Sun Xie-Fan Fang Zeng-Yun An Zhi-Shu Huang~* lian-quan gu~* School of Pharmaceutical Sciences,Sun Yat-sen University,guangzhou 510275,China

＜正＞Vascular endothelial growth factor（VEGF）is probably the most important angiogenesis inducer,and over-expression of VEGF and its receptors promote blood vessel formation which may be related with tumor *** have been reported that specific G-quadruplex structures could be formed by the G-rich sequence within the human VEGF promoter region,raising the possibility

关键词： G-quadruplex VEGF quindoline derivatives anti-angiogenic

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Mechanism on Novel Rutaecarpine Analogue Potently Reducing Lipid Accumulation in Adipocytes

Mechanism on Novel Rutaecarpine Analogue Potently Reducing L...

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第八届全国化学生物学学术会议

作者： Ying Chun Chen Xiao Yi Zeng Yan He Hong Liu Bin Wang Han Zhou Jian-Wen Chen Pei-Qing Liu lian quan gu Ji Ming Ye Zhi-Shu Huang School of Pharmaceutical Sciences and Institute of Medicinal Chemistry Sun Yat-sen University Molecular Pharmacology for Diabetes Group Health Innovations Research Institute and School of Health SciencesRMIT University

Obesity results from expansion of adipose tissue which due to an increase in adipocyte number (adipogenesis)and adipocyte size(lipogenesis).Thus inhibition of these process has been reported to be an potential anti-obetic ***(Rut)and its novel analogues(R17 and R18) were identified as strong inhibitors of lipid accumulation with little cytotoxicity via 3T3-L1 adipocytes-based ***,R17 and R18 exhibited much more potent inhibitory effects(EC=0.34±0.10μM and 1.90±0.21μM)compared to Rut(EC=8.48±1.27μM).

关键词： rutaecarpine 3T3-L1 adipogenesis lipogenesis UPR AMPK

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Molecular Dynamics Simulation of a Ligand Binding to G-Quadruplex with Different Binding modes

Molecular Dynamics Simulation of a Ligand Binding to G-Quadr...

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2011年全国药物化学学术会议——药物的源头创新

作者： Jin-Qiang Hou,Shuo-Bin Chen,Jia-Heng Tan,Tian-Miao Ou,lian-quan gu and Zhi-Shu Huang~* School of Pharmaceutical Sciences,Sun Yat-sen University,guangzhou,510006,People''s Republic of China.

＜正＞G-quadruplexes are higher-order DNA ＆ RNA structures formed from guanine-rich sequences and have recently emerged as a new class of potential molecular targets for anticancer drugs. Understanding the three-dimensional interactions between small-molecule ligands and their G-quadruplex targets in solution is the key for rational drug design and effective G-quadruplex ligand *** ligand design efforts have to date focused in large part on the G-quartet ***,ligands binding to the loop nucleotides were also observed from crystallography *** is still unclear that whether ligand could stably bind to loop nucleotides in solution states and how ligands in such binding mode impact on the stability of G-quadruplex ***,we also aim to elucidate how ligands in distinct binding modes influence the G-quadruplex ***,from crystal structure,different ligand-binding models were built and simulated by molecular dynamics *** on a series of computational analyses, the results suggested that ligand binding to the loop was viable in aqueous solution,which was depended on the particular rearrangement of *** ligands binding to the loops had negative impact on the G-quadruplex stability,whereas the ligands binding to the G-quartets had positive impact on the G-quadruplex ***,the ligands simultaneously binding to the quartets and loops had the best stabilizations effect on the G-quadruplex *** findings can help to understand the structural role of ligands with different binding modes in G-quadruplex stability and assist in the design of selective and effective G-quadruplex ligands.

关键词： Molecular dynamics simulation G-Quadruplex G-quartet Naphthalene diimide derivative

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Discovery of Novel Anti-tumour Agents for Specific Recognizing the G-quadruplex in 5'-Untranslated Region of Human Vascular Endothelial Growth Factor(hVEGF)

Discovery of Novel Anti-tumour Agents for Specific Recognizi...

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第九届全国核糖核酸学术讨论会

作者：王世珂 Yue Wu Xiao-Qin Wang guo-Tao Kuang Qi Zhang Giulia Biffi Shu-Ling Lin Hui-Yun Liu Jia-Heng Tan Zhi-Shu Huang lian-quan gu Tian-Miao Ou 中山大学药学院 School of Pharmacy Guangdong Medical College Cancer Research UK Cambridge Institute University of CambridgeLi Ka Shing Centre

Angiogenesis is important in tumorigenesis and tumor *** vascular endothelial growth factor(h VEGF)is an angiogenic growth factor that plays a crucial role in tumor *** G-rich region within the 5’-untranslated region(5’-UTR)of h VEGF m RNA can form a‘switchable’RNA G-quadruplex structure that is essential for a cap-independent translation *** firstly screen our small-molecule library for binders of this *** a result,a novel quinazoline derivative compound 1shows a significant specific interaction with the G-tract and destabilizes the Gquadruplex *** experiments results reveal that compound 1 downregulates h VEGF translation,and significantly impedes tumor cells *** also find thatcompound1exhibitsan obvious tumor inhibiting activity in MCF-7 xenograft tumors,which may relate with its ability to reduce h VEGF *** findings provide a new way of h VEGF translational control through interacting with Gquadruplex structure in the 5’UTRby small molecules.

关键词： VEGF translational regulation G-quadruplex quinazoline derivative antitumor

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