Method: Two new series of 4-styryl-7-oxycoumarin derivatives 3a-i and 4-styryl-7-
oxycoumarinyl 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
H2O2 treated 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.