In silico, in vitro antioxidant and density functional theory based structure activity relationship studies of plant polyphenolics as prominent natural antioxidants

Abstract

In the present study, different extracts of stem bark of Shorea tumbuggaia and roots of Syzygium alternifolium were screened for total phenolic content (TPC), total flavonoid content (TFC) and in vitro DPPH radical scavenging activity to isolate the natural antioxidants. The bioassay-guided fraction of stem bark of Shorea tumbuggaia yielded three compounds, piceatannol (ST-1), resveratrol-12-C-β-d-glucopyranoside (ST-2) and hopeaphenol (ST-3). Similarly, a systematic phytochemical examination of extracts of Syzygium alternifolium roots had resulted five compounds, 5,7,8,5′-tetramethoxy-3′,4′-methylenedioxyflavone (SA-1), 5-hydroxy-4′,7-dimethoxy-6,8-di-C-methylflavone (SA-2), quercetin 7-methylether (SA-3), kaempferol 7,4′-dimethylether 3-O-β-d-glucopyranoside (SA-4) and taxifolin 3-O-α-l-rhamnopyranoside (SA-5). Structures of the isolates were established using UV, IR, Mass, 1H and 13C NMR spectral studies. Density Functional Theory (DFT) calculations, Molecular docking and Lipinski rule of five were conducted to explored the antioxidant activity of isolated compounds. SA-3 (37.52 µg/mL) and ST-1 (42.43 µg/mL) showed highest IC50 values compared to the Ascorbic acid (45.97 µg/mL) and have highest electron affinities (EA eV) along with smallest HOMO-LUMO energy gap. Molecular docking and binding affinity studies with NADPH and SPSB2 proteins, revealed the prominent antioxidant activity of SA-3 and ST-1 with molecular interaction besides promising solvation energies. Hence, the two compounds maybe useful for the treatment of oxidative damage related diseases. Keywords: Antioxidants, DFT, Flavonoids, Radical Scavenging activity, Shorea tumbuggaia, Syzygium alternifolium