Synthesis and anti-oxidant activity evaluation of (±)-Anastatins A, B and their analogs.

Two novel flavonoids (±)-Anastatins A and B as well as 14 analogs, which containing a benzofuran moiety, were synthesized by using halogenation, Suzuki coupling reaction and an oxidation/Oxa-Michael reaction cascade as the key steps. The structures of the new flavonoids were confirmed by 1H NMR, 13C NMR and HRMS. The antioxidant activities of them as well as the key intermediates were evaluated by ferric reducing antioxidant power (FRAP) assay and the active compounds were evaluated in the PC12 cell model of hydrogen peroxide (H2O2)-induced oxidative damage. SAR studies suggested that, for in vitro antioxidant activity, aurone derivatives showed better bioactivity than flavone counterparts. However, cyclization to benzofuran and connecting the two conjugated parts as a whole conjugated system by a double bond diminished the in vitro antioxidant activity. Among them, the most potent compound 24c was significantly decreased H2O2-caused cell injury. The apoptotic rate (Annexin V+) of H2O2-damaged PC12 cells was 60.7% while that of the compound 24c-treated cells decreased to 5.9% and 4.1% at 10 μM and 100 μM respectively.