Novel 3-O-glycosyl-3-demethylthiocolchicines as ligands for glycine and gamma-aminobutyric acid receptors.
New 3-O-glycosyl-3-demethylthiocolchicines containing natural and unnatural sugar moieties were prepared and tested on gamma-aminobutyric acid (GABA) and strychnine-sensitive glycine receptors present in rat brain and spinal cord. Two different synthetic approaches were used with the readily available 3-O-demethylthiocolchicine (1b) and thiocolchicoside (2a). Glycosyl compounds 2a-g were obtained from 1b and 1-fluorosugars 4. 6'-Heterosubstituted glycosyl compounds 6-12 and the 6'-desoxy derivative 2h were prepared from 2a.
Gelmi
Maria Luisa
ML
Istituto di Chimica Organica "A. Marchesini", Facoltà di Farmacia, Università di Milano, Via Venezian 21, 20133 Milano, Italy. marialuisa.gelmi@unimi.it
Fontana
Gabriele
G
Pocar
Donato
D
Pontremoli
Guido
G
Pellegrino
Sara
S
Bombardelli
Ezio
E
Riva
Antonella
A
Balduini
Walter
W
Carloni
Silvia
S
Cimino
Mauro
M
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D009118:Muscimol / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013329:Structure-Activity Relationship; D013331:Strychnine / Q000494:pharmacology
D006027:Glycosides; D008024:Ligands; D018079:Receptors, GABA; D018009:Receptors, Glycine; D009118:Muscimol; D013331:Strychnine; D003078:Colchicine