Abstract
The 2-arylsulfonylaminobenzothiazole derivatives 1-27 were prepared using a one step reaction. The in vitro inhibitory activity of the compounds against protein tyrosine phosphatase 1B (PTP-1B) was evaluated. Compounds 4 and 16 are rapid reversible (mixed-type) inhibitors of PTP-1B with IC(50) values in the low micromolar range. The most active compounds (4 and 16) were docked into the crystal structure of PTP-1B. Docking results indicate potential hydrogen bond interactions between the nitro group in both compounds and the catalytic amino acid residues Arg 221 and Ser 216. Both compounds were evaluated for their in vivo antihyperglycemic activity in a type 2 diabetes mellitus rat model, showing significant lowering of plasma glucose concentration, during the 7h post-intragastric administration.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Benzothiazoles / chemical synthesis
-
Benzothiazoles / chemistry*
-
Benzothiazoles / pharmacology
-
Blood Glucose / drug effects
-
Computer Simulation
-
Diabetes Mellitus, Experimental / blood
-
Diabetes Mellitus, Experimental / drug therapy
-
Diabetes Mellitus, Type 2 / blood
-
Diabetes Mellitus, Type 2 / drug therapy
-
Disease Models, Animal
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology*
-
Hypoglycemic Agents / chemical synthesis
-
Hypoglycemic Agents / chemistry*
-
Hypoglycemic Agents / pharmacology
-
Kinetics
-
Male
-
Models, Molecular
-
Protein Binding
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
-
Rats
-
Rats, Wistar
-
Structure-Activity Relationship
Substances
-
Benzothiazoles
-
Blood Glucose
-
Enzyme Inhibitors
-
Hypoglycemic Agents
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1