117680-09-8Relevant articles and documents
Synthetic Mimics of Native Siderophores Disrupt Iron Trafficking in Acinetobacter baumannii
Banas, Victoria S.,Bohac, Tabbetha J.,Fang, Luting,Giblin, Daryl E.,Wencewicz, Timothy A.
, p. 2138 - 2151 (2021/07/07)
Many pathogenic bacteria biosynthesize and excrete small molecule metallophores, known as siderophores, that are used to extract ferric iron from host sources to satisfy nutritional need. Native siderophores are often structurally complex multidentate chelators that selectively form high-affinity octahedral ferric iron complexes with defined chirality recognizable by cognate protein receptors displayed on the bacterial cell surface. Simplified achiral analogues can serve as synthetically tractable siderophore mimics with potential utility as chemical probes and therapeutic agents to better understand and treat bacterial infections, respectively. Here, we demonstrate that synthetic spermidine-derived mixed ligand bis-catecholate monohydroxamate siderophores (compounds 1-3) are versatile structural and biomimetic analogues of two native siderophores, acinetobactin and fimsbactin, produced by Acinetobacter baumannii, a multidrug-resistant Gram-negative human pathogen. The metal-free and ferric iron complexes of the synthetic siderophores are growth-promoting agents of A. baumannii, while the Ga(III)-complexes are potent growth inhibitors of A. baumannii with MIC values 1 μM. The synthetic siderophores compete with native siderophores for uptake in A. baumannii and maintain comparable apparent binding affinities for ferric iron (KFe) and the siderophore-binding protein BauB (Kd). Our findings provide new insight to guide the structural fine-tuning of these compounds as siderophore-based therapeutics targeting pathogenic strains of A. baumannii.
Spermexatin and Spermexatol: New Synthetic Spermidine-Based Siderophore Analogues
Sharma, Sushil K.,Miller, Marvin J.,Payne, Shelley M.
, p. 357 - 367 (2007/10/02)
Syntheses of hexanediamine-based dihydroxamate (Hexamate), spermidine-based trihydroxamate (Spermexatins), and spermidine-based mixed siderophore analogues (Spermexatols) are described.Key intermediates include the N-hydroxysuccinimide esters of various hydroxamic acids, e.g., malonohydroxamate, succinohydroxamate, and glutarohydroxamate.These intermediates were synthesized, characterized, and incorporated as the ligating chains on spermidine.Also, mixed iron chelating compounds (Spermexatols) with both catechol and hydroxamic acid side chains were synthesized.Thereagent carbobenzoxyimidazole was employed to distinguish between the primary and secondary amino groups of spermidine.The ability of these iron chelators to stimulate microbial growth is also described.
