Synthesis of glycosyl derivatives as dopamine prodrugs:: interaction with glucose carrier GLUT-1

被引:69
作者
Fernández, C
Nieto, O
Fontenla, JA
Rivas, E
de Ceballos, ML
Fernández-Mayoralas, A
机构
[1] CSIC, Inst Cajal, E-28002 Madrid, Spain
[2] CSIC, Inst Quim Organ Gen, E-28006 Madrid, Spain
[3] Univ Santiago de Compostela, Dept Farmacol, Fac Farm, Santiago De Compostela 15782, Spain
关键词
D O I
10.1039/b212066f
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Glucosyl dopamine (DA) derivatives may represent a new class of DA prodrugs that would interact with glucose transporter GLUT-1, present in the blood-brain barrier, and generate DA in the brain. Therefore, compounds bearing the sugar moiety linked to either the amino group or the catechol ring of DA through amide, ester, carbamate, peptide or glycosidic bonds were synthesized. The behavior of the compounds as prodrugs was monitored in different media and the affinity of the glycoconjugates for the glucose carrier GLUT-1 using human erythrocytes was also studied. Most of the compounds were markedly stable in buffer and plasma, and several compounds released DA when incubated with brain extracts and the rate was related to the bond linking DA with glucose. The new glucosyl conjugates substituted at the C-6 position of the sugar were more potent inhibitors of glucose transport when compared to C-1 and C-3 substituted derivatives. This work provides structure-activity information about the interaction of substituted glucose with the GLUT-1 transporter.
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页码:767 / 771
页数:5
相关论文
共 25 条
[1]  
AUDUS KL, 1992, ADV DRUG RES, V23, P1
[2]   MAMMALIAN PASSIVE GLUCOSE TRANSPORTERS - MEMBERS OF AN UBIQUITOUS FAMILY OF ACTIVE AND PASSIVE TRANSPORT PROTEINS [J].
BALDWIN, SA .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1154 (01) :17-49
[3]   THE USE OF L-DOPA IN PARKINSONS-DISEASE - A 20 YEAR FOLLOW-UP [J].
BARBEAU, A .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1981, 2 (11) :297-299
[4]   STRUCTURAL REQUIREMENTS FOR BINDING TO SUGAR-TRANSPORT SYSTEM OF HUMAN ERYTHROCYTE [J].
BARNETT, JEG ;
HOLMAN, GD ;
MUNDAY, KA .
BIOCHEMICAL JOURNAL, 1973, 131 (02) :211-221
[5]   EVIDENCE FOR 2 ASYMMETRIC CONFORMATIONAL STATES IN HUMAN ERYTHROCYTE SUGAR-TRANSPORT SYSTEM [J].
BARNETT, JEG ;
HOLMAN, GD ;
CHALKLEY, RA ;
MUNDAY, KA .
BIOCHEMICAL JOURNAL, 1975, 145 (03) :417-429
[6]   PROGRESS IN PARKINSONS-DISEASE [J].
CALNE, DB .
NEW ENGLAND JOURNAL OF MEDICINE, 1984, 310 (08) :523-524
[7]   REGIOSELECTIVE MANIPULATION OF HYDROXYL-GROUPS VIA ORGANOTIN DERIVATIVES [J].
DAVID, S ;
HANESSIAN, S .
TETRAHEDRON, 1985, 41 (04) :643-663
[8]   Synthesis and biological activity of beta-glucuronyl carbamate-based prodrugs of paclitaxel as potential candidates for ADEPT [J].
deBont, DBA ;
Leenders, RGG ;
Haisma, HJ ;
vanderMeulenMuileman, I ;
Scheeren, HW .
BIOORGANIC & MEDICINAL CHEMISTRY, 1997, 5 (02) :405-414
[9]   ANOTHER APPROACH TO THE SYNTHESIS OF BENZYL DERIVATIVES OF REDUCING MONOSACCHARIDES - STUDY OF PYRANOSE-FURANOSE EQUILIBRIA BY C-13 NMR [J].
DECOSTER, E ;
LACOMBE, JM ;
STREBLER, JL ;
FERRARI, B ;
PAVIA, AA .
JOURNAL OF CARBOHYDRATE CHEMISTRY, 1983, 2 (03) :329-341
[10]   Synthesis and biological studies of glycosyl dopamine derivatives as potential antiparkinsonian agents [J].
Fernández, C ;
Nieto, O ;
Rivas, E ;
Montenegro, G ;
Fontenla, JA ;
Fernández-Mayoralas, A .
CARBOHYDRATE RESEARCH, 2000, 327 (04) :353-365