Hydroxamate siderophores: Natural occurrence, chemical synthesis, iron binding affinity and use as Trojan horses against pathogens

Abstract

Hydroxamic acids are an important class of molecules, in particular because of their metal-chelating ability. Microorganisms, including pathogenic bacteria, use hydroxamate-based entities (siderophores), among others, to acquire Fe (III). The "Trojan horse" strategy exploits the need of bacteria for this metal by using Fe (III) active transporters to carry antibacterial or bactericidal moieties into the bacterial cell. Many natural Trojan horses (sideromycins) are derived from hydroxamic acids, thereby reflecting their potency. Various artificial sideromycins and their antibacterial activities have been reported. This review discusses the structural aspects of the hydroxamate-siderophores isolated in the last two decades, the chemical synthesis of their building blocks, their binding affinity towards Fe (III), and their application as Trojan horses (weaknesses and strengths).

Antifungal Siderophore Conjugates for Theranostic Applications in Invasive Pulmonary Aspergillosis Using Low-Molecular TAFC Scaffolds

“…It is possible to use these siderophores as a “Trojan horse” to smuggle all kinds of molecules into bacteria [ 42 ]. The recently approved drug Cefiderocol (Fetroja ® ) by the FDA (November 2019) is the first artificial sideromycin on the market consisting of a catechol-chelating unit and a cephalosporin antibiotic (beta-lactam) against Gram-negative bacteria [ 43 ].…”

Antifungal siderophore conjugates for theranostic applications in invasive pulmonary aspergillosis using low molecular TAFC scaffolds

“…It is possible to use these siderophores as a "Trojan horse" to smuggle all kinds of molecules into bacteria [42]. The recently approved drug Cefiderocol (Fetroja ® ) by the FDA (Nov 2019) is the first artificial sideromycin on the market consisting of a catechol chelating unit and a cephalosporin antibiotic (beta-lactam) against gram-negative bacteria [43].…”

Cyclopeptide Derivatives from the Sponge-Derived Fungus Acremonium persicinum F10

“…Recently, ASP2397 (also known as VL-2397 under clinical trial), a hydroxamate-containing siderophore isolated from fungus Acremonium persicinum, exhibited potent antifungal activities [6,19]. Hydroxamic acids usually possess a formula RC(O)N(OH)R' and can be regard as a type of N-hydroxy amides [20]. Here, elucidation of acremonpeptide E; acremonpeptide F; and their complexes with Al 3+ , Fe 3+ , and Ga 3+ (1-8) further enrich the chemical structural diversity of the hydroxamate siderophore family.…”