Antidiabetic activity of N-(6-substituted-1,3-benzothiazol-2-yl)benzenesulfonamides.
N-(6-Substituted-1,3-benzothiazol-2-yl)benzenesulfonamide derivatives 1-8 were synthesized and evaluated for their in vivo antidiabetic activity in a non-insulin-dependent diabetes mellitus rat model. Several compounds synthesized showed significant lowering of plasma glucose level in this model. As a possible mode of action, the compounds were in vitro evaluated as 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors. The most active compounds (3 and 4) were docked into the crystal structure of 11beta-HSD1. Docking results indicate potential hydrogen bond interactions with catalytic amino acid residues.
Moreno-Díaz
Hermenegilda
H
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
Villalobos-Molina
Rafael
R
Ortiz-Andrade
Rolffy
R
Díaz-Coutiño
Daniel
D
Medina-Franco
Jose Luis
JL
Webster
Scott P
SP
Binnie
Margaret
M
Estrada-Soto
Samuel
S
Ibarra-Barajas
Maximiliano
M
León-Rivera
Ismael
I
Navarrete-Vázquez
Gabriel
G
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D013449:Sulfonamides; D000096926:Benzenesulfonamides