Antimicrobial activity of Tetrapleura tetraptera (Uyayak) extracts, ADMET profiling and molecular docking of its bioactive compounds against dihydropteroate synthase of Escherichia coli

AbstractBackgroundEscherichia colilike otherEnterobactericeaeare frequent isolates implicated in food-borne diseases. The prevalence of multi-drug resistantE. coliisolates from street vended fruits and its salad is on the increase across Nigeria. This study was designed to evaluate the antimicrobial activityTetrapleura tetraptera(Uyayak) againstE. colias well as the druggability and pharmacokinetics of its bioactive compounds using in-silico and in-vitro approaches. Methods We utilized previously reported standard protocols in the isolation, characterization and the identification of the isolates, and the collection and preparation of theT. tetrapterapods. Antimicrobial activity of the extracts was done using the Kirby-Bauer disc diffusion method. Resulting bioactive compounds from gas chromatography coupled to mass spectrophotometry (GC-MS) were converted into canonical stings and used to for target prediction in humans and ADMET properties using the SWISSADME and pkCSM tools. Bioactive compounds that met Lipinski’s rule of five (ROF) were subjected to molecular docking against dihydropteroate synthase ofE. coliusing the AutoDock vina tool and the resulting interactions visualized in 2-D via Biovia Discovery Studio 21. Results The GC-MS analysis returned a total of twenty-eight (28) bioactive compounds. The abundance of theE. coliisolates varied according to location and fruit types. At trimethoprim and extracts concentrations of < 100mg/ml and < 100% respectively, the isolates showed resistance. A total of 13 bioactive compound showed zero violations to Lipinski’s rule of five (ROF). ADMET analysis of the screened bioactive compounds showed favourable absorption (intestinal and water solubility) and toxicity (AMES and hepatoxicity) profiles than trimethoprim. Molecular docking revealed various amino residues interacting with dihydropteroate synthase and gave docking scores that ranged from − 4.0 to -5.3 kcal/mole for the bioactive compounds and − 6.5 5 kcal/mole for trimethoprim. Target prediction showed that all the bioactive are capable of reaching various targets with nuclear receptor being the most abundant target. Conclusion The bioactive compounds ofT. tetrapteraexamined in this study showed favourable antimicrobial activity againstE. coli, docking scores and pharmacokinetics, suggesting the need for further studies to validate their potential as antimetabolites for management of pathogenicE. coliinfections.