Phytochemical Investigations, Antibacterial and Antioxidant Activities, and In Silico Molecular Docking Studies of Stem Bark Constituents of Dodonaea angustifolia L. f

Abstract

Plant derived therapies that mitigate infectious disease and oxidative stress may be beneficial in the treatment of wide range of diseases. D. angustifolia is commonly known as Hitacha in Afan Oromo, Kitkita in Amharic, traditionally used for the treatment of variety conditions. This study was aimed to identify antibacterial and antioxidant compounds from the extracts of D. angustifolia. In view of this, stem bark of D. angustifolia was extracted with dichloromethane and dichloromethane:methanol (1:1) and the later extract was further partitioned. The dichloromethane extract after silica gel column chromatography afford six compounds identified as stigmasterol (45), stigmasterol derivatives (46), 2-hydroxy-3-(stearoyloxy) propanoic acid (47), 2,3-dihydroxypropyl stearate (48), stearic acid (49) and hexacosane (50). The structures of the isolated compounds were characterized using NMR spectroscopic techniques. Additionally, five compounds previously isolated from ethyl acetate leaves extract of D. angustifolia, including 2-hydroxy-15,16-epoxyceloda-3,13(16),14-trien-18-oic acid (6), santin (25), pinocembrin (26), 5,7,4′-trihydroxy-3,6-dimethoxyflavone (28) and 5,6,5′-trihydroxy-3,7,4’-trimethoxyflavone (51) were included herein for bioassay and in silico computational studies. The antibacterial and antioxidant activities were evaluated using agar disc diffusion method against four strains of bacteria and DPPH methods, respectively. The antibacterial evaluation showed highest activity with the aqueous methanol soluble portion of stem bark extract against E. coli (13.00±2.52 mm at 100 mg/mL); compound 45 against P. aeruginosa (13.33±0.88 mm); pinocembrin (26) against E. coli and S. pyogenes (12.67±0.88 mm and 11.00±0.58 mm) and compound 28 against S. aureus (12.00±1.00 mm) each at 2 mg/mL, compared with ciprofloxacin (ranging from 16.83±0.70  21.67±1.20 mm at 30 μg/mL). The highest percent inhibition of the DPPH radical were observed with aqueous methanol soluble portion (IC50: 13.15 μg/mL); pinocembrin (26) (IC50: 0.089 μg/mL), compared with ascorbic acid (IC50 of 0.11 μg/mL). Molecular docking study was done using Auto-Dock Vina, where pinocembrin (26) and compound 45 exhibited highest binding affinity (-8.1 and -7.4 kcal/mol) with the target DNA gyrase B and Santin (25) (-5.1 kcal/mole) with S. aureus pyruvate kinase. Additionally, compounds 6, 25, 26, 28, 45 and 51 showed higher binding affinity with the target human peroxiredoxins 5. The current study revealed that the plant is promising source of antimicrobial and antioxidant compounds which support the traditional use of D. angustifolia for the treatment of infections