Ultrasound-promoted copper-catalyzed synthesis of bis-arylselanyl chrysin derivatives with boosted antioxidant and anticancer activities.
Abstract Herein we report the use of ultrasonic irradiation (US) in the synthesis of six new semi-synthetic selenium-containing chrysin derivatives by a simple and effective methodology utilizing CuI as catalyst, in good to excellent yields (60–89%). It was observed that US accelerates the reaction compared to conventional heating with excellent selectivity for diselenylated products. Compounds were tested for their antioxidant and anticancer activities in vitro and it was observed that the presence of selenium in the A-ring of chrysin enhanced both antioxidant and anticancer properties. Semi-synthetic 6,8-bis( o -tolylselanyl)-chrysin 3b has the best radical scavenging activity of DPPH (I max : 39.79 µM) and ABTS + (IC 50 : 6.5 µM) radicals. Similarly, in the Reactive Species (RS) assay, 3b showed high antioxidant activity in mice cortex (IC 50 : 5.67 µM), whereas 6,8-bis( p -anisoylselanyl)-chrysin 3c was the more active in the hippocampus (IC 50 : 5.63 µM). The Se-chrysins were effective in prevention of lipid peroxidation, highlighting 6,8-bis( p -fluorophenylselanyl)-chrysin 3d in cortex (IC 50 : 0.54 µM) and 3b in hippocampus (IC 50 : 0.27 µM). In addition, 3d was effective in inhibiting human lung adenocarcinoma (A549) cells growth, with a IC 50 of 19.9 µM after 72 h of treatment, while 6,8-bis( p -anisoylselanyl)-chrysin 3c presented the higher antiproliferative activity after 48 h of treatment (IC 50 of 41.4 µM).