Heggemann Susanne, Möllmann Ute, Gebhardt Peter, Heinisch Lothar
Hans Knöll-Institut für Naturstoff-Forschung, Jena, Germany.
Biometals. 2003 Dec;16(4):539-51. doi: 10.1023/a:1023476214838.
New trishydroxamates and triscatecholates based on methyl alpha-D-glucopyranoside, methyl alpha-D-galactopyranoside, methyl alpha-D-ribopyranoside and methyl alpha-D-xylopyranoside as well as on 1,3,5-tri-O-benzyl-myo-inositol were synthesized. N-Methylsuccinohydroxamate, N-methylglutarohydroxamate and their O-benzoyl derivatives were used as hydroxamate moieties. 2,3-Dihydroxybenzoyl derivatives and acylated compounds as well as 2,3- and 3,4-dihydroxybenzylidenehydrazino derivatives, partly with spacer groups, were utilized as catecholate components. The siderophore activity of the prepared siderophore analogues was examined by a growth promotion assay with various Gram-negative bacteria and mycobacteria and by the CAS-assay. Some trishydroxamates and triscatecholates showed siderophore activity on Gram-negative bacteria and triscatecholates on mycobacteria. Iron complexes of the trishydroxamates act as siderophores for all types of iron transport mutants. The recognition and uptake specificity of these compounds was studied by E. coli siderophore receptor and iron transport mutants. Structure activity correlations are discussed.
合成了基于α-D-吡喃葡萄糖苷甲酯、α-D-吡喃半乳糖苷甲酯、α-D-吡喃核糖苷甲酯和α-D-吡喃木糖苷甲酯以及1,3,5-三-O-苄基-myo-肌醇的新型三异羟肟酸酯和三儿茶酚酸酯。N-甲基琥珀酰异羟肟酸酯、N-甲基戊二酰异羟肟酸酯及其O-苯甲酰基衍生物被用作异羟肟酸部分。2,3-二羟基苯甲酰基衍生物、酰化化合物以及2,3-和3,4-二羟基亚苄基肼基衍生物（部分带有间隔基团）被用作儿茶酚酸成分。通过对各种革兰氏阴性菌和分枝杆菌的生长促进试验以及CAS试验，检测了所制备的铁载体类似物的铁载体活性。一些三异羟肟酸酯和三儿茶酚酸酯对革兰氏阴性菌表现出铁载体活性，而三儿茶酚酸酯对分枝杆菌表现出铁载体活性。三异羟肟酸酯的铁络合物对所有类型的铁转运突变体都起铁载体的作用。通过大肠杆菌铁载体受体和铁转运突变体研究了这些化合物的识别和摄取特异性。讨论了构效关系。
