Control of Multidrug-Resistant Hospitalized Pathogenic Bacteria Using the Secondary Metabolites of Calotropis procera and In-silico Analysis of Bacterial Virulent Proteins
Abstract:
This study explores the multidrug-resistant pattern of
hospitalized pathogens and their pharmacological impact against the secondary
metabolites isolated from Calotropis procera, for its medicinal properties. Moreover,
this study implies that comprehensive analysis, including isolation of
multidrug-resistant hospitalized bacterial species and extraction and
characterization of secondary metabolites by GC-MS from Calotropis procera, molecular
docking, ADMET profiling, and, was conducted to evaluate the therapeutic
potential of these compounds. The multidrug-resistant Klebsiella pneumonia,
Salmonella typhi, and Pseudomonas aeruginosa were isolated and they also showed
sensitivity against C. procera leaf extract. GC-MS reveals the key volatile
compounds, including oleic acid, and the molecular docking with the proteasome
(PDB ID: 5JXG) identified 5-Methyl-2-phenylindolizine as the most promising
compound due to its high binding affinity (-6.7 kcal/mol), with
2,6-Dimethylphenol, 3,5-Dimethylaniline, and Ethyl Heptanoate showing progressively
lower affinities. Interaction analysis highlighted the importance of PRO266,
TRP531, GLU271, and ARG490 residues. ADMET profiling revealed that 2,6-dimethylphenol
and 3,5-Dimethylaniline have favorable absorption and minimal CYP interactions,
while 5-methyl-2-phenylindolizine demonstrated excellent absorption and BBB
permeability. Additionally, the study found that C. procera metabolites could
target furin, a proprotein convertase involved in bacterial virulence, offering
a novel approach to combat multidrug-resistant bacterial infections. These
findings underscore the potential of Calotropis procera metabolites as
effective therapeutic agents and active against multidrug-resistant bacterial
species.
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