Phytochemical Analysis, Biological Evaluation and Docking Study of Root Extracts of Brucea antidysenteric

Abstract

Natural products have been a source of medicinal agents since thousands of years and remarkable numbers of modern drugs have been derived from natural sources. Brucea antidysentrica, commonly known as Aballo (Amharic) and Qomonyo (in Afan Oromo), was used to treat various diseases such as leprosy, wound, diarrhea, fever, eye disease, rabies and cancer. The roots of Brucea antidysentrica were extracted by dichloromethane/methanol (1:1), methanol (100%) and acid-base extraction protocol to give 12.77g, 9.4g and 5.1g (3.65 %, 2.68 % and 1.46 %) yields, respectively. Phytochemical screening analysis conducted on roots extracts of B. antidysentrica showed the presence of alkaloid, tannins, flavonoids, steroids and saponins, terpenoids, and phytosterols. Silica gel column chromatographic separation of the crude extract (mixture of CH2Cl2: MeOH (1:1) and MeOH, acid-base) afforded a known βcarboline alkaloid, flazin methyl ether derivative (1), and indole alkaloids, canthin-6-one (2), and 1,11-dimethoxycanthin-6-one (3) of which the first two compounds are isolated for the first time from the species. The structures of compounds were characterized using spectroscopic methods (IR, 1H NMR, 13C NMR, DEPT-135, COSY, HSQC and HMBC). The extracts and isolated compounds were also evaluated in vitro for their antibacterial activities using disc diffusion method against E. coli, S. aureus, B. subtilis and S. thphimurium. Strong inhibition zone values (12.6±0.60 and 12.5±0.87 mm for alkaloid 2 and 3) were observed against E. coli and S. thphimurium compared to standard ciprofloxacin (27.3±2.52 and 29±1.00 mm). The radical scavenging activity of dichloromethane/methanol (1:1), acid-base extract, and alkaloids 1-3 were 83.3 %, 80%, 85.3 %, 87.5 % and 78.4 % at 100 µg/mL, respectively. Suggesting that compound 1 and 2 displayed slightly highest radical scavenging activity indicating the potential of the plant as herbal remedies. The molecular docking data showed flazin methyl ether derivative (1) and 1,11-dimethoxycanthin-6-one (3) were found to show hydrogen bond interaction with active site amino acid residues PHE196 and ALA 51 at a distance of 1.5 Ao. Hydrophobic interactions were observed between 2 and 3 with VAL201, LYS57, GLY200, ASN198, ALA51, LEU52, and ASN198, LEU52, VAL201, LYS57, respectively, suggesting the compounds may act as potential inhibitors of DNA gyrase enzyme.