Synthesis and biological evaluation of benzimidazole derivatives as potent AMP-activated protein kinase activators.
Design, synthesis and structure-activity relationships of benzimidazole derivatives as activators of the AMP-activated protein kinase (AMPK) are presented in this paper. AMPK is the central component of a protein kinase cascade that plays a key role in the regulation of energy balance. Once activated, AMPK initiates a series of responses that are aimed at restoring the energy balance of the cell and recent studies have indicated that AMPK plays an important role in regulation of the whole-body energy metabolism. The following study based on the lead compound S27847 involved modification of three regions of this compound. Preliminary structure-activity relationships are being described.
Charton
Julie
J
UMR CNRS 8525, Universite de Lille II, Institut de Biologie et Institut Pasteur de Lille, France. julie.charton@univ-lille2.fr
Girault-Mizzi
Sophie
S
Debreu-Fontaine
Marie-Ange
MA
Foufelle
Fabienne
F
Hainault
Isabelle
I
Bizot-Espiard
Jean-Guy
JG
Caignard
Daniel-Henri
DH
Sergheraert
Christian
C
D055372:AMP-Activated Protein Kinases; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001681:Biological Assay; D003510:Cyclohexanes / Q000737:chemistry*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D009097:Multienzyme Complexes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001562:Benzimidazoles; D003510:Cyclohexanes; D009097:Multienzyme Complexes; C512501:S27847; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases