Synthesis of Oleanolic Acid Dimers as Inhibitors of Glycogen Phosphorylase

被引：34
|
作者：
Cheng, Keguang [1 ,2 ]
Liu, Jun [3 ]
Sun, Hongbin [1 ]
Xie, Juan [2 ]
机构：
[1] China Pharmaceut Univ, Ctr Drug Discovery, Coll Pharm, Nanjing 210009, Peoples R China
[2] UniverSud, CNRS, ENS Cachan, PPSM, F-94230 Cachan, France
[3] China Pharmaceut Univ, Jiangsu Ctr Drug Screening, Nanjing 210038, Peoples R China
来源：
CHEMISTRY & BIODIVERSITY | 2010年 / 7卷 / 03期
关键词：
PENTACYCLIC TRITERPENES; ALLOSTERIC SITE; DERIVATIVES; DISCOVERY; TARGET; DRUG;
D O I：
10.1002/cbdv.200900086
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Recently, oleanolic acid was found to be an inhibitor of glycogen phosphorylase. For further structural modification, we have synthesized several dimers of oleanolic acid by using amide, ester, or triazole linkage with click chemistry. The click chemistry was shown to be the most efficient method for the dimer synthesis. Nearly quantitative yield of triazole-linked dimers was obtained. Biological evaluation of the synthesized dimers as inhibitors of glycogen phosphorylase has been described. Four of six dimers exhibited inhibitory activity against rabbit muscle glycogen phosphorylase a (RMGPa), with compounds 2 and 7 as the most potent inhibitors, which displayed an IC50 value (ca. 3 mu M) lower than that of oleanolic acid (IC50=14 mu M).
引用
收藏
页码：690 / 697
页数：8
相关论文
共 50 条
  • [21] Pentacyclic triterpenes. Part 2: Synthesis and biological evaluation of maslinic acid derivatives as glycogen phosphorylase inhibitors
    Wen, XA
    Zhang, P
    Liu, J
    Zhang, LY
    Wu, XM
    Ni, PZ
    Sun, HB
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (03) : 722 - 726
  • [22] Optimization of anthranilimide based glycogen phosphorylase inhibitors: Replacement of the naphthoic acid core
    Sparks, Steven M.
    Banker, Pierette
    Thomson, Stephen
    Peat, Andrew
    Tavares, Francis
    Garrido, Dulce
    Cooper, Joel
    Dickerson, Scott
    Weiel, Jim
    Bickett, Mark
    Boucheron, Joyce
    Wang, Tony
    Clancy, Daphne
    Nolte, Robert
    Wang, Liping
    Golden, Pamela
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2010, 239
  • [23] Synthesis of (benzimidazol-2-yl)aniline derivatives as glycogen phosphorylase inhibitors
    Galal, Shadia A.
    Khattab, Muhammad
    Andreadaki, Fotini
    Chrysina, Evangelia D.
    Praly, Jean-Pierre
    Ragab, Fatma A. F.
    El Diwani, Hoda I.
    BIOORGANIC & MEDICINAL CHEMISTRY, 2016, 24 (21) : 5423 - 5430
  • [24] Novel thienopyrrole glycogen phosphorylase inhibitors: Synthesis, in vitro SAR and crystallographic studies
    Whittamore, Paul R. O.
    Addie, Matthew S.
    Bennett, Stuart N. L.
    Birch, Alan M.
    Butters, Michael
    Godfrey, Linda
    Kenny, Peter W.
    Morley, Andrew D.
    Murray, Paul M.
    Oikonomakos, Nikos G.
    Otterbein, Ludovic R.
    Pannifer, Andrew D.
    Parker, Jeremy S.
    Readman, Kristy
    Siedlecki, Pawel S.
    Schofield, Paul
    Stocker, Andy
    Taylor, Melvyn J.
    Townsend, Linda A.
    Whalley, David P.
    Whitehouse, Jennifer
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (21) : 5567 - 5571
  • [25] Glucopyranose spirohydantoins: Specific inhibitors of glycogen phosphorylase
    delaFuente, C
    Krulle, TM
    Watson, KA
    Gregoriou, M
    Johnson, LN
    Tsitsanou, KE
    Zographos, SE
    Oikonomakos, NG
    Fleet, GWJ
    SYNLETT, 1997, (05) : 485 - &
  • [26] Iminosugars: Potential inhibitors of liver glycogen phosphorylase
    Jakobsen, P
    Lundbeck, JM
    Kristiansen, M
    Breinholt, J
    Demuth, H
    Pawlas, J
    Candela, MPT
    Andersen, B
    Westergaard, N
    Lundgren, K
    Asano, N
    BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (03) : 733 - 744
  • [27] INHIBITORS OF GLYCOGEN PHOSPHORYLASE: IN SEARCH OF AN ANTIDIABETIC DRUG
    Watson, K. A.
    Gregoriou, M.
    Johnson, L. N.
    ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES, 1996, 52 : C250 - C250
  • [28] Optimization of anthranilimide based glycogen phosphorylase inhibitors
    Sparks, Steven M.
    Banker, Pierette
    Thomson, Stephen
    Peat, Andrew
    Tavares, Francis X.
    Sternbach, Daniel D.
    Garrido, Dulce
    Dwornik, Kate
    Cooper, Joel
    Dickerson, Scott
    Weiel, Jim
    Bickett, D. Mark
    Boucheron, Joyce
    Wang, Tony
    Clancy, Daphne
    Nolte, Robert T.
    Wang, Liping
    Golden, Pamela
    Graham, Richard
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 237
  • [29] Natural flavonoids are potent inhibitors of glycogen phosphorylase
    Jakobs, S
    Fridrich, D
    Hofem, S
    Pahlke, G
    Eisenbrand, G
    MOLECULAR NUTRITION & FOOD RESEARCH, 2006, 50 (01) : 52 - 57
  • [30] Glucopyranose Spirohydantoins: Specific Inhibitors of Glycogen Phosphorylase
    Synlett, (485):
12345