Repurposing of Auranofin Against Bacterial Infections: An In silico and In vitro Study

Abstract

Aim: The aim of the study was to find out the role of auranofin as a promising broadspectrum antibacterial agent.

Methods: In vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software).

Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in the zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin-binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate the multimodal mechanism of action of auranofin. Finally, MTT assay has shown the non-cytotoxic effect of auranofin.

Conclusion: In conclusion, auranofin in combination with existing antibiotics, could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides the possibility of the use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.

Keywords: Auranofin; MVD.; Zebra fish infection model; bacterial infections; in silico studies; in vitro studies.