Search for iron complexes with potential activity via the Trojan Horse Effect in Escherichia coli

Abstract

Antimicrobial resistance of pathogens is a global problem. New chemical strategies such as the Trojan Horse effect mediated by siderophores represent a viable alternative to this problem. Microorganisms synthesize siderophores to scavenge iron from the extracellular medium and internalize it through outer membrane proteins, such as FhuA protein in Escherichia coli. Deferoxamine is a siderophore produced by Streptomyces pilosus, but iron-deferoxamine complex (FeDFO) can also be assimilated by E. coli. Promiscuity around the use of siderophores justifies the search for new iron complexes with potential affinity for FhuA. In this work we use a new database containing 86665 coordination compounds (tmQM). By means of an exploratory analysis of tmQM data and molecular docking, 4 complexes with higher chemical reactivity and affinity for FhuA than FeDFO were obtained. Hydrophobic and hydrogen bond interactions are predominant in the recognition of these complexes.