Synthetic Multimeric Heptyl Mannosides as Potent Antiadhesives of Uropathogenic Escherichia coli

被引：61
作者：
Gouin, Sebastien G. [1 ]
Wellens, Adinda [2 ]
Bouckaert, Julie [2 ]
Kovensky, Jose [1 ]
机构：
[1] Univ Picardie Jules Verne, Dept Chem, Lab Glucides, CNRS,UMR 6219, F-80039 Amiens, France
[2] Vrije Univ Brussel, B-1050 Brussels, Belgium
来源：
CHEMMEDCHEM | 2009年 / 4卷 / 05期
关键词：
antiadhesive drugs; antibiotics; E; coli; click chemistry; multivalency; URINARY-TRACT-INFECTIONS; ASSISTED CLICK CHEMISTRY; 1,3-DIPOLAR CYCLOADDITIONS; ADHESION; INHIBITORS; AFFINITY; BINDING; HEMAGGLUTINATION; ADSORPTION; TRIVALENT;
D O I：
10.1002/cmdc.200900034
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Urinary tract infections caused by uropathogenic Escherichia coli presents a serious communal and nosocomial health problem initiated by bacterial adhesion to the bladder cells. E coli expresses fimbriae with a mannose-binding adhesin, FimH, at the tip. Heptyl alpha-D-mannoside (HM) is a nanomolar inhibitor of this lectin, preventing adhesion of type 1-piliated E. coli and reducing bacteria levels in a murine cystitis model. Herein, we described the synthesis of multimeric heptyl-mannosides with valencies ranging from one to four by copper-catalyzed azide alkyne cycloaddition (CuAAC). Biological evaluation of the multivalent compounds revealed an increase in potency compared to HM. Inhibition of bladder cell binding highlighted a promising tetravalent derivative with inhibitory concentrations 6000-and 64-fold lower than mannose and HM respectively.
引用
收藏
页码：749 / 755
页数：7
相关论文
共 42 条
[1]   Synthesis of a nonavalent mannoside glycodendrimer based on pentaerythritol [J].
Al-Mughaid, H ;
Grindley, TB .
JOURNAL OF ORGANIC CHEMISTRY, 2006, 71 (04) :1390-1398
[2]   Intracellular bacterial biofilm-like pods in urinary tract infections [J].
Anderson, GG ;
Palermo, JJ ;
Schilling, JD ;
Roth, R ;
Heuser, J ;
Hultgren, SJ .
SCIENCE, 2003, 301 (5629) :105-107
[3]   Novel multivalent mannose compounds and their inhibition of the adhesion of type 1 fimbriated uropathogenic E. coli [J].
Appeldoorn, CCM ;
Joosten, JAF ;
el Maate, FA ;
Dobrindt, U ;
Hacker, J ;
Liskamp, RMJ ;
Khan, AS ;
Pieters, RJ .
TETRAHEDRON-ASYMMETRY, 2005, 16 (02) :361-372
[4]   A microwave-assisted click chemistry synthesis of 1,4-disubstituted 1,2,3-triazoles via a copper(I)-catalyzed three-component reaction [J].
Appukkuttan, P ;
Dehaen, W ;
Fokin, VV ;
Van der Eycken, E .
ORGANIC LETTERS, 2004, 6 (23) :4223-4225
[5]   Adhesion inhibition of F1C-fimbriated Escherichia coli and Pseudomonas aeruginosa PAK and PAO by multivalent carbohydrate ligands [J].
Autar, R ;
Khan, AS ;
Schad, M ;
Hacker, J ;
Liskamp, RMJ ;
Pieters, RJ .
CHEMBIOCHEM, 2003, 4 (12) :1317-1325
[6]  
Blanco JLJ, 1997, CARBOHYD RES, V303, P367, DOI 10.1016/S0008-6215(97)00176-6
[7]   CuI-catalyzed alkyne-azide "click" cycloadditions from a mechanistic and synthetic perspective [J].
Bock, VD ;
Hiemstra, H ;
van Maarseveen, JH .
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2006, 2006 (01) :51-68
[8]   Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin [J].
Bouckaert, J ;
Berglund, J ;
Schembri, M ;
De Genst, E ;
Cools, L ;
Wuhrer, M ;
Hung, CS ;
Pinkner, J ;
Slättegård, R ;
Zavialov, A ;
Choudhury, D ;
Langermann, S ;
Hultgren, SJ ;
Wyns, L ;
Klemm, P ;
Oscarson, S ;
Knight, SD ;
De Greve, H .
MOLECULAR MICROBIOLOGY, 2005, 55 (02) :441-455
[9]   Microwave assisted "click" chemistry for the synthesis of multiple labeled-carbohydrate oligonucleotides on solid support [J].
Bouillon, Camille ;
Meyer, Albert ;
Vidal, Sebastien ;
Jochum, Anne ;
Chevolot, Yann ;
Cloarec, Jean-Pierre ;
Praly, Jean-Pierre ;
Vasseur, Jean-Jacques ;
Morvan, Francois .
JOURNAL OF ORGANIC CHEMISTRY, 2006, 71 (12) :4700-4702
[10]   Silver(I) oxide mediated highly selective monotosylation of symmetrical diols.: Application to the synthesis of polysubstituted cyclic ethers [J].
Bouzide, A ;
Sauvé, G .
ORGANIC LETTERS, 2002, 4 (14) :2329-2332
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