Molecular docking analysis of antibacterial indole alkaloids from roots of Brucea antidysentrica

Abstract

Brucea antidysentrica is one of the medicinal plants used traditionally to treat various diseases such as leprosy, wound, diarrhea, fever, eye disease, rabies and tumor/cancer. Phytochemical screening test of dichloromethane/methanol (1:1) and methanol extracts revealed the presence of alkaloids, tannins, flavonoids, steroids and saponins, terpenoids, and phytosterols. Silica gel column chromatographic separation of dichloromethane/methanol (1:1) and acid-base extracts afforded compound 1, canthin-6-one (2) and 1,11-dimethoxycanthin-6-one (3). The crude extracts and isolated compounds were screened for in vitro antibacterial activity against strains of Salmonella thphimurium, Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Canthin-6-one (2) and 1,11-dimethoxycanthin-6-one (3) exhibited promising antibacterial activity against E. coli and S. thphimurium (12.6±0.6 and 12.5±0.87 mm zone of inhibition, respectively) compared to ciprofloxacin (27.3±2.52 and 29±1.00 mm, respectively), at 0.5 mg/mL. The radical scavenging activity of dichloromethane/methanol (1:1) and acid-base extract were 83.3 % and 80 %, respectively, whereas alkaloids 1-3 displayed activity of 85.3 %, 87.5 % and 78.4 % at 100 µg/mL, respectively, suggesting that canthin-6-one (2) displayed promising radical scavenging activity. The molecular docking analysis showed compound 1 and 1,11-dimethoxycanthin-6-one (3) were found to show hydrogen bond interaction with active site amino acid residue PHE196 and ALA 51 at a distance of 1.5 A^o and 1.5 A^o, respectively. 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.