| 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. | |
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MedLine Citation:
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PMID: 12705174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Lothar Heinisch; Steffen Wittmann; Thomas Stoiber; Ina Scherlitz-Hofmann; Dorothe Ankel-Fuchs; Ute Möllmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arzneimittel-Forschung Volume: 53 ISSN: 0004-4172 ISO Abbreviation: Arzneimittelforschung Publication Date: 2003 |
Date Detail:
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Created Date: 2003-04-22 Completed Date: 2003-05-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372660 Medline TA: Arzneimittelforschung Country: Germany |
Other Details:
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Languages: eng Pagination: 188-95 Citation Subset: IM |
Affiliation:
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Hans Knöll-Institute for Natural Product Research, Jena, Germany. Heinisch@pmail.hki-jena.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acylation 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 |
| Chemical | |
Reg. No./Substance:
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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
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