Synthesis and antioxidant potential of some biscoumarin derivatives

Abstract

Purpose: To synthesize and screen some 3-substituted-bis-2H-chromen-2t-ones in a search for possible new antioxidants for use in food and pharmaceuticals industries. Methods: 2-Hydroxycoumarin was allowed to react with various substituted aromatic aldehydes in the presence of base as a catalyst to obtain to obtain 3-substituted-bis-2H-chromen-2t-ones. The chemical structures of the synthesized compounds were confirmed by Fourier transform infra-red (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR), mass spectrometry (MS) and elemental analysis. The synthesized biscoumarin derivatives were screened by three parallel antioxidant assays, namely, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, reducing power, and linoleic acid lipid peroxidation. Further, the half minimal inhibitory concentration (IC50) of the compounds was also determined. Butylatedhydroxy toluene (BHT) was used as a standard reference in the antioxidant assay. Results: A library of ten biscoumarin analogues (3a-3j) were synthesized and evaluated for their antioxidant potential. The highest DPPH activity was shown by 3,3'-(3-hydroxy-4-methoxyphenylmethylene)-bis-4-hydroxy-2H-chromen-2-one (3g) and 3,3'-(4-methoxyphenyl-methylene)-bis-4-hydroxy-2H-chromen-2-one (3h) with IC50 values of 53.33 ± 6.12 and 68.44 ± 2.67 µg/mL, respectively, compared to the standard compound BHT (butylatedhydroxy toluene) with IC50 of 71.00 ± 0.82 µg/mL. The strongest inhibition of linoleic acid peroxidation was by 3,3'-(3-hydroxy-4-methoxyphenylmethylene)-bis-4-hydroxy-2H-chromen-2-one (3g) and 3'-(4-hydroxy-3-methoxyphenyl-methylene)-bis-4-hydroxy-2H-chromen-2-one (3d) with inhibition values of 70.34 and 69.87%, respectively. Compound 3g demonstrated the highest reducing power with an absorbance of 0.49 at 10 mg/mL concentration (p < 0.001). It was observed that the change in substitution greatly affected the antioxidant potential of the compounds, with the presence of the methoxy group at position-4 of aryl moiety along with 2-hydroxycoumarin being critical for antioxidant activity.Conclusion: The synthesized biscoumarin derivatives, 3g and 3h, are superior antioxidants to standard (BHT) and are suitable lead molecules for further development.