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Abstract

New artificial catecholate siderophores with methyl alpha-D-glucopyranoside as scaffold were synthesized. The dihydroxy- or di(acetoxy)benzoyl moieties were attached either directly or via aminopropyl spacer groups, to the carbohydrate scaffold. The siderophore activity of the prepared siderophore analogs was examined by a growth promotion assay using various Gram-negative bacteria and mycobacteria and by the CAS-assay.

Synthesis of carbohydrate-based artificial siderophores and their biological applications

“…36 More recently, analogues of siderophores with cyclic monosaccharide backbone were synthesized and characterized, showing Fe(III) chelating capabilities that are comparable, if not greater than those of their natural counterparts; biologically, they are highly promising synthetic analogues, as in vivo studies show significant siderophore activity indicating favorable cell receptor recognition and cellular uptake. [13][14][15][16]37,38 The design of siderophore mimics requires some important features to be considered, which include the nature of donor groups, denticity, chelate ring size, architecture, hydrophobicity/ hydrophilicity and stability. The availability of different stereoisomeric forms of saccharides and their high functionality render them particularly attractive for the conception of siderophore model compounds of varying structure and polarity and the construction of an optimal octahedral binding cavity for the Fe(III) ion.…”

“…In 2001, Heggemann et al have shown that carbohydrates can substitute advantageously the trilactone structure of enterobactin. 14,16 In the last decade, the synthesis of carbohydrate-based artificial siderophores was focused only on monosaccharide scaffolds. The group synthesized several glucose derivatives with two or three 2,3-di(acetoxy)benzoyl ligands at secondary carbon positions of the glucopyranose ring and also with three 2,3-di(acetoxy)phenoxyacetyl and 8-acetoxy-2-oxo-3,4-dihydro-2H-benzo [1,3]oxazin-3-yl)acetyl ligands at the same positions.…”

“…15 New dihydroxybenzylidenehydrazino derivatives based on methyl a-Dglucopyranoside by replacing the aminopropyl groups by hydrazinocarbonylethyl functional groups have been reported as a new variation of the carbohydrate siderophores (Scheme 7). …”

“…14 Scheme 3 Synthesis of a triscatecholate derivative with free catechol-OH groups. 16 characterised by the decreased production of normal haemoglobin and resulting in anaemia. Desferichrome (4, Fig.…”

“…11,12 Several studies of artificial siderophores have been reported during the last two decades. 3,5,[13][14][15][16][17][18][19][20] These compounds attracted growing interest as clinically useful iron chelators for the treatment of iron overload diseases and for iron transport-mediated antibiotics or antimicrobial compounds; 5 they are also useful antimalarial agents, acting by causing iron deprivation of malaria parasites. 21 The most common moieties used in artificial siderophores are catecholate and hydroxamate groups.…”