Document Detail

Synthesis and biological activity of tris- and tetrakiscatecholate siderophores based on poly-aza alkanoic acids or alkylbenzoic acids and their conjugates with beta-lactam antibiotics.
MedLine Citation:
PMID:  12705174     Owner:  NLM     Status:  MEDLINE    
New linear and tripodal tri-aza- and tetra-aza alkanoic acids or alkylbenzoic acids were prepared as basic structures for siderophore mimetics from polyamines and oxocarbonic acids or formylbenzoic acids by catalytic hydrogenation. From these acids acetylated tris- and tetrakiscatecholates or 8-acyloxy-2,4-dioxo-benzoxazine derivatives as well as compounds with spacer groups were synthesized. These derivatives were coupled with ampicillin, amoxicillin, bacampicillin or cefaclor to new siderophore antibiotic conjugates. Most of the catecholate derivatives showed high siderophore activities in strains of Pseudomonas aeruginosa and Escherichia coli in a growth promotion assay under iron limitation conditions. The beta-lactam conjugates were highly active in vitro against Gram-negative bacteria correlating to the siderophore activity of the catecholate moiety and depending on the beta-lactam part. One ampicillin conjugate based on 5-(aminoethyl)-2,5,8-triazaalkylbenzoic acid was highly active against Gram-negative and Gram-positive bacteria. It was shown that conjugates with enhanced activity against Gram-negative bacteria use active iron uptake routes to penetrate the bacterial outer membrane barrier. Correlations between structure and biological activity were studied.
Lothar Heinisch; Steffen Wittmann; Thomas Stoiber; Ina Scherlitz-Hofmann; Dorothe Ankel-Fuchs; Ute Möllmann
Related Documents :
2848804 - Epr-detectable redox centers of the periplasmic hydrogenase from desulfovibrio vulgaris.
9216684 - Effect of copper and iron ions on cytotoxicity induced by ascorbate, gallate and caffeate.
18964754 - Determination of cobalt, nickel, lead, bismuth and indium in ores, soils and related ma...
18962704 - Silver-reductor method for determination of iron in iron ores and iron-ore sinters.
3923884 - 15-hydroxyeicosatetraenoic acid is a potent inflammatory mediator and agonist of canine...
16169094 - The connections between c75 and obesity drug-target pathways.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  53     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  2003  
Date Detail:
Created Date:  2003-04-22     Completed Date:  2003-05-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  188-95     Citation Subset:  IM    
Hans Knöll-Institute for Natural Product Research, Jena, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amides / chemical synthesis*,  pharmacology*
Ampicillin / chemical synthesis,  pharmacology
Anti-Bacterial Agents / chemical synthesis*,  chemistry,  pharmacology
Bacteria / drug effects*
Benzoic Acids / chemical synthesis,  pharmacology
Catechols / chemical synthesis*,  pharmacology*
Indicators and Reagents
Microbial Sensitivity Tests
Siderophores / chemical synthesis*,  chemistry,  pharmacology
Reg. No./Substance:
0/Amides; 0/Anti-Bacterial Agents; 0/Benzoic Acids; 0/Catechols; 0/Indicators and Reagents; 0/Siderophores; 69-53-4/Ampicillin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  In vitro assay for the screening of the plaque-reducing activity of antimicrobial agents.
Next Document:  Synthesis and biological evaluation of N-substituted alpha-amino acids from 4-hydroxy coumarins.