Synthesis and structure-activity relationship study of antidiabetic penta-O-galloyl-D-glucopyranose and its analogues

Journal of Medicinal Chemistry
Yulin RenXiaozhuo Chen

Abstract

The rapid increase of obesity-associated diabetes has created urgent demands for more effective antidiabetic therapies and pharmaceuticals that are able to address the problems of hyperglycemia and weight gain simultaneously. Our previous studies indicated that the alpha- and beta-anomers of penta-O-galloyl-D-glucopyranose (PGG), 2 and 3, act as insulin mimetics that bind to and activate the insulin receptor, stimulate glucose transport in adipocytes, and reduce blood glucose and insulin levels in diabetic and obese animals. In addition, they inhibit differentiation of preadipocytes into adipocytes. These activities suggest that 2 and 3 may reduce blood glucose without increasing adiposity. To investigate the structure-activity relationship of 2 and 3, four series of novel compounds were prepared and their glucose transport stimulatory activities were measured using a radioactive glucose uptake bioassay. The assay results indicate that both the glucose and the galloyl groups are critical to the activity of 2 and 3. It appears that the glucose core provides an optimal scaffold to present the galloyl groups with the correct spatial orientation to induce activity. Moreover, the galloyl groups linked to the 1, 2, 3, and 4 positions...Continue Reading

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Citations

Jun 15, 2011·Apoptosis : an International Journal on Programmed Cell Death·Yanyan CaoXiaozhuo Chen
May 9, 2012·Journal of Medicinal Chemistry·Carlos TurradoMaría L López-Rodríguez
Nov 12, 2009·Organic Letters·Anna B WilliamsJohn A Katzenellenbogen
Dec 22, 2010·Antimicrobial Agents and Chemotherapy·Mei-Hui LinShih-Tung Liu
Feb 18, 2014·Journal of Natural Medicines·Yanyan CaoXiaozhuo Chen
Sep 15, 2010·Molecular Aspects of Medicine·Mar LarrosaFrancisco A Tomás-Barberán
May 7, 2013·Cryobiology·Chikako KuwabaraSeizo Fujikawa
Aug 21, 2016·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xiujuan XiYouqing Shen
Feb 3, 2009·Chemical & Pharmaceutical Bulletin·Kosuke DodoYuichi Hashimoto
Sep 10, 2015·Magnetic Resonance in Chemistry : MRC·Serge LavoieAndré Pichette
Oct 10, 2018·Annals of Biomedical Engineering·Sourav S PatnaikEnder A Finol
Dec 24, 2018·Nutrients·Phiwayinkosi V DludlaSithandiwe E Mazibuko-Mbeje
Dec 1, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shota MachidaTaketo Uchiyama
Mar 5, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Xiaozhuo ChenAili Guo
May 1, 2021·International Journal of Molecular Sciences·Tovit Rosenzweig, Sanford R Sampson
Jul 3, 2021·International Journal of Molecular Sciences·Shiyao ZhangSiyu Chen
Nov 28, 2012·ACS Medicinal Chemistry Letters·Yulin RenJianhua Yu
Apr 10, 2013·The Journal of Organic Chemistry·Naoki MichihataHidetoshi Yamada
Apr 10, 2019·Journal of Medicinal Chemistry·Elisa G-DoyagüezMichael S Rogers
Dec 3, 2021·Chemical & Pharmaceutical Bulletin·Shota MachidaTaketo Uchiyama

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