Isoflavones as modulators of adenosine monophosphate-activated protein kinase

Adenosine monophosphate-activated protein kinase (AMPK) is expressed in all eukaryotic cells and can therefore be found in vertebrates, invertebrates, and plants. Since AMPK participates in the regulation of homeostasis on various levels, small compounds that can modulate AMPK activity could be valuable research tools. Several flavonoids can modulate AMPK. Here we investigated the modulatory effect of 37 isoflavones on AMPK activity using an in vitro kinase assay. Because the relationship between the structural properties of flavonoids and their modulatory activities has not been elucidated yet, we used comparative molecular field analysis to derive the structural conditions for modulation of AMPK activity. The molecular binding mode of isoflavones to AMPK was elucidated using in silico docking studies. The findings presented here can aid in the design of new modulators with better specificity for AMPK.