Antidiabetic activity of N-(6-substituted-1,3-benzothiazol-2-yl)benzenesulfonamides

Bioorg Med Chem Lett. 2008 May 1;18(9):2871-7. doi: 10.1016/j.bmcl.2008.03.086. Epub 2008 Apr 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • Amino Acid Sequence
  • Benzenesulfonamides
  • Binding Sites
  • Blood Glucose / metabolism
  • Cell Line
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrogen Bonding
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / pharmacology*
  • Kidney / cytology
  • Kidney / drug effects*
  • Models, Chemical
  • Molecular Sequence Data
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / pharmacology*

Substances

  • Blood Glucose
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Sulfonamides
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1