Antibacterial Activity, Phytochemical Analysis of C. coggygria Leaf Extracts Against S. typhi, and Computational Studies to Screen Potential Drug Candidates

Abstract

Typhoid fever is a serious infectious disease caused by Salmonella typhi and Salmonella Paratyphi A. Although there are several drugs available for the treatment of Salmonella infection, however, the rising cases of bacterial resistance against common drugs necessitate new drug discovery against S. typhi. So Typhoid fever can be managed in a better way. Therefore we carried out the phytochemical analysis of Cotinus coggygria by FTIR and GC–MS analysis followed by antibacterial activity against S. typhi. Moreover, We also conducted molecular docking to find out important phytochemicals; methanol (48 compounds) and ethyl acetate (66 compounds) and 6 molecular targets; glycosidehydrolase (PDB Id: 4hzm), OmpF (PDB Id; 4kra), DNA gyrase (PDB Id;5ZTJ), AvrA (PDB Id; 6BE0), RamR (PDB Id; 6IE9), and tryptophan Synthase (PDB Id; 7L03). Results show that the ethyl acetate extracts of C. coggygria have the highest antibacterial activity against S. typhi, with inhibition zones ranging from 23 ± 2.8 to 18 ± 0.5 mm at different concentrations as compared to methanol extracts. Based on the docking score, DNA gyrase (5ZTJ) was found as the most suitable molecular target. DNA gyrase (5ZTJ). Further molecular dynamics simulation study resulted in 7 potential inhibitors from ethyl acetate extract and 5 potential inhibitors from methanol extracts as they had lower free binding energy than the reference drug ciprofloxacin. Based on this study we conclude that the top four phytochemicals that may be used for therapeutic purposes and drug development against salmonella activity are Lanosterol, Lup-20(29)-en-3-one, 9,19-Cyclolanost-24-en-3-ol, (3. beta.)-), and Periplogenin acetate.

Graphical Abstract