Probing antioxidant activity of 2'-hydroxychalcones: Crystal and molecular structures, in vitro antiproliferative studies and in vivo effects on glucose regulation
Abstract
In order to better understand the antioxidant behavior of a series of polyphenolic 2'-hydroxychalcones, we describe the results of several chemical and biological studies, in vitro and in vivo. Single crystal X-ray methods elucidated their molecular structures and important intermolecular interactions such as Hbonding and molecular stacking in the crystal structures that contribute to our knowledge in explaining antioxidant activity.
The results of experiments using the 1,1-diphenyl-2-dipicrylhydrazyl (DPPH) UV vis spectroscopic method indicate that a hydroxyl group in position 5' induces the highest antioxidant activity. Consequently, 2,2',5'-trihydroxychalcone was selected for further study in vitro towards ROS scavenging in L-6 myoblasts and THP-1 human monocytes, where it shows an excellent antioxidant activity in a concentration range lower than that reported by most studies of related molecules.
In addition, this chalcone shows a very selective activity: it inhibits the proliferation of leukemic cells, but it does not affect the normal L-6 myoblasts and human fibroblasts. In studying 2,2',5'-trihydroxychalcone's effect on weight gain and serum glucose and insulin levels in Zucker fatty (fa(-)/fa(-)) rats we found that supplementing the diet with a 10 mg/kg dose of this chalcone (3 times weekly) blunted the increase in glucose that co-occurs with weight gain over the 6-week treatment period.
It is concluded that 2,2',5'-trihydroxychalcone has the potential to serve as a protective agent for some debilitating diseases.