Studies and Syntheses of Siderophores, Microbial Iron Chelators, and Analogs as Potential Drug Delivery Agents

John   M.   Roosenberg II; Yun-Ming      Lin; Yong      Lu; Marvin   J.   Miller

Abstract

Siderophores (microbial iron chelators) play an extremely important role in microbial pathogenicity. Microbial uptake of siderophore-iron complexes through active transport systems allow microbes to survive and proliferate even under iron deficient environments during invasion of a host. Due to their structural complexity, unique iron (III) chelation, acquisition properties, and their therapeutic potential, siderophores have attracted much attention in a broad range of disciplines. Tremendous progress has been made in siderophore syntheses, in determination of the structures and functions of outer membrane receptors (e.g. FhuA and FepA), and in the mechanistic insight into siderophore-iron-mediated active transport processes. One of the important practical applications of this active transport system is development of species-selective active drug transport (the Trojan Horse approach) to potentially treat infections due to drug resistant strains of microbes. Siderophore-drug conjugates have shown great potential in active drug delivery to target pathogenic microbes.

Keywords: synthsese, siderophores, microbial iron chelators, analogs, potential drug delivery agents, membrane receptors, FhuA, FepA, alcaligenes denitrificans, alcaligenes xylosoxidans, bordetella, pertussis, bronchiseptica, bisucaberin, alteromonas haloplanktis, antitumor agents, rhizobium meliloti, nannocytis exedens, vibrio parahaemolyticus, yersiniabactin entercolitica, smegmatis, neoaurm, tuberculosis, M avium, natural sideropphores