Synthesis, molecular docking and dynamics simulation studies of new 7-oxycoumarin derivatives as potential antioxidant agents.

METHOD: Two new series of 4-styryl-7-oxycoumarin derivatives 3a-i and 4-styryl-7-oxycoumarin-8-Mannich bases 6a-r were designed and synthesized. Ten compounds were evaluated for their antioxidant activity in vitro against DPPH and in vivo against lipid peroxidation, superoxide dismutase (SOD), glutathione-s-transferase (GST) and catalase (CAT) activities. Molecular modeling study was performed to predict the mode of binding of the target compounds in the binding site.

RESULTS & CONCLUSION: Although the tested compounds showed moderate to low dose dependent DPPH inhibition activities in vitro, most of them displayed remarkable antioxidant effects in vivo. Compounds 1, 6b, 3c and 6r displayed significant decrease in MDA, SOD and CAT enzyme levels in H2O2treated rats. Free binding energy was estimated by docking, MM-PBSA and MM-GBSA. Molecular dynamics simulation followed by MM-GBSA calculation was correlated to the antioxidant effect. Compound 1 illustrated the highest MM-GBSA value (-20.38) and the best antioxidant effect.