Identification of potential inhibitors from Andrographis paniculata bioactive compounds against extended-spectrum β-lactamases through in silico and in vitro approaches

The present study aims to identify potential medicinal plant-based extended-spectrum β-lactamase (ESBL) inhibitors from Andrographis paniculata using both in silico and in vitro approaches. The ESBLs were obtained from the protein data bank. The structures of phytoconstituents were obtained from the PubChem database. The compounds were docked against different ESBLs (targeted proteins) using AutodockTools followed by molecular dynamics simulation. In silico results were further validated using in vitro testing through the disc diffusion method. The molecular docking revealed that most of the phytoconstituents have a good binding affinity. The binding energy and in vitro study of the phytoconstituents of Andrographis paniculata were compared with the standard inhibitor for ESBL i.e. clavulanic acid .14- Acetylandrographolide (AAD) showed good binding with the ESBL proteins, having the best values reported in the docking with OXA-10. Simulation of the complex of AAD and OXA-10 showed that the complex was relatively steady as evidenced by the lack of sudden fluctuations in the values of root mean square deviations, the radius of gyration and solvent-accessible surface area. Further confirmation of the in silico approach was done by an in vitro study against ESBL-producing organisms which showed inhibitory results. From this study, we can conclude that A.paniculata may have the potential to inhibit ESBLs and may be considered for treating bacterial infections.