Investigation of The Efflux Pump Inhibitory Potential of Hexacontane Against AcrB Protein by Molecular Docking and ADMET Analysis

Abstract

Reported that approximately 700,000 deaths occur worldwide each year due to bacterial resistance(1,2). According to the World Health Organization report in early 2017, a list of antibiotic-resistant microorganisms was published, and this list includes the Enterobacteriaceae family, which is one of those considered highly pathogenic(3,2). Antibiotic resistance occurs after a complex process involving multiple mechanisms, and the efflux pump is only one of these mechanisms(4,2). The RND efflux pump is also a mechanism from the superfamily class(5,6,7). The RND efflux pump is an AcrAB-TolC complex protein containing AcrA, AcrB and TolC protein(8,9,7). Efflux pump inhibitors can inactivate drug transport or can be used to restore the effectiveness of resistant antibiotics(10,2). However, their clinical use is not yet suitable due to toxicity11. In this study, the potential inhibitory property of the hexacontane (67.34%) component in the methanol extract of the macrofungus Fomes fomentarius against the AcrB protein (RND efflux pump) was investigated by molecular docking method, the binding relationship between the protein and ligand and in silico study and ADMET analysis.
Keywords: Efflux pumps, molecular docking, efflux pumps inhibitors, antibiotic resistance, AcrB, hexacontane
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