74272-81-4Relevant academic research and scientific papers
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.
Chemical synthesis and biological evaluation of gallidermin-siderophore conjugates
Yoganathan, Sabesan,Sit, Clarissa S.,Vederas, John C.
experimental part, p. 2133 - 2141 (2011/05/14)
The lantibiotic gallidermin was modified at lysine residues by regioselective attachment of derivatives of pyochelin, agrobactin and desferrioxamine B with the objective of having siderophore receptors of Gram-negative bacteria transport the antibiotic-iron chelator conjugate through the outer membrane. All of the conjugates retained activity against the Gram-positive indicator strain, Lactococcus lactis subsp. cremoris HP. However, testing of the conjugates against several Gram-negative strains yielded unexpected results. Bacteria treated with 100 μM of the conjugates complexed with Fe3+ grew better than bacteria grown in iron-free media but worse than bacteria grown in the same media supplemented with 10 μM FeCl 3. Although these findings indicate that the conjugates are unable to inhibit the growth of Gram-negative bacteria, they indicate penetration of the outer membrane and provide structure-activity information for design of other lantibiotic conjugates. The synthetic strategy is applicable for linking biomarkers or fluorescence probes to gallidermin for studies on its localization and mode of action. As there are many lantibiotics that operate with unknown mechanisms of action, this chemical approach provides a means to modify such peptides with biomarkers for biological investigations.
Significance of asymmetric sites in choosing siderophores as deferration agents
Bergeron,Mei Gou Xin,Weimar,Smith,Wiegand
, p. 2469 - 2478 (2007/10/03)
The syntheses of the microbial iron chelators L-fluviabactin, its unnatural enantiomer, D-fluviabactin, L-homofluviabactin, and L-agrobactin, are described. The key steps involve the selective bis-acylation of the terminal nitrogens of norspermidine, sper
Ruthenium-Catalyzed Oxidations of Alcohols
Murahashi,Naota
, p. 203 - 213 (2007/10/03)
A combination of low-valent ruthenium complexes and peroxides such as t-BuOOH and peracids serves as efficient catalytic systems for the oxidation of aromatic and aliphatic hydroxy compounds. The utility of these methods was demonstrated by the synthesis of acyl cyanides which are versatile synthetic intermediates. The principle of the catalytic oxidations with peracids lead to the novel and efficient method for aerobic oxidation of alcohols in the presence of aldehydes. This reaction is of importance in synthetic and large scale industrial processes and from environmental points of view. The present principle will provide new chemistry of oxidative transformations of various industrially important functional materials.
Ruthenium-catalyzed oxidations for selective syntheses of ketones and acyl cyanides. Selective acylation of amino compounds with acyl cyanides
Murahashi,Naota
, p. 433 - 440 (2007/10/02)
Oxidation of alcohols to the corresponding carbonyl compounds with tert-butyl hydroperoxide in the presence of dichlorotris(triphenylphosphine)ruthenium catalyst gives the corresponding carbonyl compounds with high efficiency. This method can be applied to the oxidation of cyanohydrins to give acyl cyanides which are versatile synthetic intermediates. Acylation of amino compounds with acyl cyanides thus obtained proceeds chemoselectively. Thus, the reaction of amino alcohols with acyl cynides gives N-acylated products exclusively. In the similar N-acylation of polyamines primary amines are selectively acylated in the presence of secondary amines. These reactions are highly useful for the synthesis of spermidine and spermine alkaloids such as spermidine alkaloids such as spermidine siderophores. Dimeric cyclocoupling reaction of diacyl cyanides such as iso- and terephthaloyl cyanides with polyamines can be performed under the similar reaction conditions to give the corresponding polyazamacrocycles with high efficiency.
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.
Synthesis of Parabactin Analogues and Formation of Transition Metal Complexes of Parabactin and Related Compounds
Miyasaka, Tadayo,Nagao, Yoshimitsu,Fujita, Eiichi,Sakurai, Hiromu,Ishizu, Kazuhiko
, p. 1542 - 1550 (2007/10/02)
Transition metal complexes of parabactin and its related synthetic spermidine catecholamides which lack the central o-hydroxyphenyloxazoline were studied by the potentiometric titration method, e.s.r. spectroscopy, and fast atom bombardment mass spectrometry (FAB-MS).Direct mass spectral sampling of the parabactin-Fe(III) complex in glycerol solution was first achieved by FAB-MS spectrometry, confirming that the composition of the parabactin-Fe(III) complex is (2-)*2Na(1+) and that the iron(III) ion binds with two catechols and an o-hydroxyphenyl-Δ2-oxazoline moiety in NaOH solution.The e.s.r. g value (4.5) of the parabactin-Fe(III) complex differed from those (4.3) of the 3:1 catechol-Fe(III) complex and other parabactin-related catecholamide-Fe(III) complexes.These results suggest that the structure of the parabactin-Fe(III) complex differs considerably from the regular octahedral structure of the 3:1 catechol-Fe(III) complex and may have a structure similar to the ferrimycobactin P-Fe(III) complex, in which the iron(III) lies exposed in a splayed V-shaped cleft and binds with five oxygens and one nitrogen in a very strained octahedron.
