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
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Research Support, Non-U.S. Gov't
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
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Amino Acid Sequence
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Benzenesulfonamides
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Binding Sites
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Blood Glucose / metabolism
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Cell Line
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Humans
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Hydrogen Bonding
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Hypoglycemic Agents / chemical synthesis
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Hypoglycemic Agents / pharmacology*
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Kidney / cytology
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Kidney / drug effects*
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Models, Chemical
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Molecular Sequence Data
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / pharmacology*
Substances
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Blood Glucose
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Enzyme Inhibitors
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Hypoglycemic Agents
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Sulfonamides
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11-beta-Hydroxysteroid Dehydrogenase Type 1