Aryl O- and S-galactosides and lactosides as specific inhibitors of human galectins-1 and -3: role of electrostatic potential at O-3.
Phase transfer catalyzed reaction was used for the high yielding synthesis of aryl 1-thio-beta-d-galacto- and lacto-pyranosides carrying a panel of substituents on the phenyl groups. Best galectin-1 inhibitors were simple p-nitrophenyl thiogalactoside 5a for the monosaccharide and o-nitrophenyl thiolactoside 6f or napthylsulfonyl lactoside 8c, both being 20 times better relative to natural ligands. Relative inhibitory properties as low as 2500 and 40 microM were observed, respectively. The electronic effects of the lactoside aglycons directly influenced the electrostatic potential at O-3, which was associated with the inhibitory potencies against galectin-1.
Giguère
Denis
D
Departement of Chemistry, Université du Québec à Montréal, PO Box 8888, Succ. Centre-Ville Montreal, Québec, Canada H3C 3P8.
Sato
Sachiko
S
St-Pierre
Christian
C
Sirois
Suzanne
S
Roy
René
R
D018360:Crystallography, X-Ray; D005697:Galactosides / Q000494:pharmacology*; D037483:Galectin 1 / Q000037:antagonists & inhibitors*; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D055672:Static Electricity; D013329:Structure-Activity Relationship
D005697:Galactosides; D037483:Galectin 1; D037502:Galectin 3; D006027:Glycosides; C445499:LGALS1 protein, human; C008245:lactosides