Antimicrobial effects of novel siderophores linked to β-lactam antibiotics

Kline, Toni; Fromhold, M; McKennon, T.E; Cai, Shuangqi; Treiberg, Jennifer; Ihle, N; Sherman, David R.; Schwan, William R.; Hickey, Mark J.; Warrener, Paul; Witte, Pamela R.; Brody, Linnea L.; Goltry, L.; Barker, L. M.; Anderson, S.U; Tanaka, Shigefumi; Shawar, Ribhi; Nguyen, Lisa Y.; Langhorne, Michael H.; Bigelow, Alan W.; Embuscado, L; Naeemi, E

doi:10.1016/s0968-0896(99)00261-8

Cited by 40 publications

(32 citation statements)

References 54 publications

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“…The mixture was stirred for 16 h, diluted with EtOAc (50 mL), washed with H 2 O (20 mL) and brine (20 mL), dried over Na 2 SO 4 , and concentrated in vacuo. 17 The crude product was purified directly by column chromatography on silica gel using hexane–EtOAc (10:1) as the eluent to give 7 as a white solid (15 mg, 69% over two steps). 1 H NMR (CDCl 3 ) δ 10.5 (s, 1H), 8.06 (d, J = 8.0 Hz, 2H), 8.03 (dd, J = 8.0, 4.0 Hz, 1H), 7.56 (dd, J = 8.0, 4.0 Hz, 1H), 7.38 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 2.76 (q, J = 8.0 Hz, 2H), 1.31 (t, J = 8.0 Hz, 3H); 13 C NMR (CDCl 3 ) δ 174.1, 167.1, 158.1, 148.4, 135.1, 128.5, 127.8, 127.6, 123.1, 120.1, 117.7, 108.2, 28.9, 15.3; HPLC purity 99.8%; MS (ESI) m / z 267 (M + H) + .…”

Section: Methodsmentioning

confidence: 99%

“…The oxadiazole 23 was prepared from 1a by cyclodehydration in the presence of hydroxylamine hydrochloride and sodium acetate (Scheme 5). 17 Reaction of 2-(benzyloxy)aniline ( 24 ) with ethyl 3-chloro-3-oxopropanoate gave the intermediate 25 , which was readily hydrolyzed to the carboxylic acid 26 . 13 This intermediate was converted to the final bis-amide 28 through amide bond formation 13 with 4-ethylaniline and subsequent deprotection (Scheme 5).…”

Section: Chemistrymentioning

confidence: 99%

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Synthesis, Biological Evaluation, and Structure–Activity Relationships of N-Benzoyl-2-hydroxybenzamides as Agents Active against P. falciparum (K1 strain), Trypanosomes, and Leishmania

et al. 2012

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In our efforts to identify novel chemical scaffolds for the development of new antiprotozoal drugs, a compound library was screened against T. gondii tachyzoites with activity discovered for N-(4-ethylbenzoyl)-2-hydroxybenzamide 1a against T. gondii as described elsewhere.1 Synthesis of a compound set was guided by T. gondii SAR with 1r found to be superior for T. gondii, also active against Thai and Sierra Leone strains of P. falciparum, and with superior ADMET properties as described elsewhere.1 Herein, synthesis methods and details of the chemical analysis of the compounds in this series are described. Further, this series of N-benzoyl-2-hydroxybenzamides was re-purposed for testing against four other protozoan parasites: T. b. rhodesiense, T. cruzi, L. donovani, and P. falciparum (K1 isolate). Structure-activity analyses led to the identification of compounds in this set with excellent anti-leishmanial activity (compound 1d). Overall, compound 1r was the best and had activity 21-fold superior to that of the standard anti-malarial drug chloroquine against the K1 P. falciparum isolate.

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Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Synthesis, Biological Evaluation, and Structure–Activity Relationships of N-Benzoyl-2-hydroxybenzamides as Agents Active against P. falciparum (K1 strain), Trypanosomes, and Leishmania

et al. 2012

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“…Bacterial growth was affected by the siderophore-antibiotic conjugates and the effect was enhanced if an iron chelator (like EDDA) was added to the growth media. Siderophore-β-lactam conjugates have also been of interest (16). Cephalosporin conjugated to a siderophore was tested against different pathogenic bacteria including E. coli, P. aeruginosa and S. aureus.…”

Section: Pharmacological and Medical Applicationsmentioning

confidence: 99%

Biotechnology of siderophores in high-impact scientific fields

Serrano

2017

Biomolecular Concepts

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Different aspects of bacterial and fungal siderophore biotechnological applications will be discussed. Areas of application presented include, but are not limited to agriculture, medicine, pharmacology, bioremediation, biodegradation and food industry. In agriculture-related applications, siderophores could be employed to enhance plant growth due to their uptake by rhizobia. Siderophores hindered the presence of plant pathogens in biocontrol strategies. Bioremediation studies on siderophores discuss mostly the mobilization of heavy metals and radionuclides; the emulsifying effects of siderophoreproducing microorganisms in oil-contaminated environments are also presented. The different applications found in literature based in medicine and pharmacological approaches range from iron overload to drug delivery systems and, more recently, vaccines. Additional research should be done in siderophore production and their metabolic relevance to have a deeper understanding for future biotechnological advances.

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“…Many cephalosporins and monobactams when covalently linked to a siderophore moiety have shown increased activity against pathogens such as E. coli and P. aeruginosa but a valid way to predict which siderophores could serve as escorting agents for -lactam antibiotics has not been found as most effective compounds lost the siderophoric abilities [182]. Evaluation of the antibacterial activity of the salmycin class of ''Trojan Horse'' antibiotics revealed that, not only the choice of drugs (in particular target location) is important, but also the linkers which will influence the drug releasability from the siderophore-drug conjugates [181].…”

Section: Antimicrobial and Antiparasitic Compoundsmentioning

confidence: 99%

Recent Achievements on Siderophore Production and Application

Carvalho¹,

Marques²,

Fernandes³

2011

BIOT

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Iron is the most abundant chemical element on Earth but its most common oxidation state is Fe(III) which presents a very low solubility under physiological conditions. During evolution, micro-organisms have developed sound strategies to acquire iron from both the environment and superior organisms, including direct uptake of iron ions from exogenous iron/heme sources and the synthesis of specialized Fe(III) chelators called siderophores. The present review paper aims at presenting and discussing the latest achievements in siderophore isolation and production, as well as novel applications of these molecules in therapies against iron-related diseases and in vaccines, and their application as antimicrobial agents and biosensors.

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Antimicrobial effects of novel siderophores linked to β-lactam antibiotics

Cited by 40 publications

References 54 publications

Synthesis, Biological Evaluation, and Structure–Activity Relationships of N-Benzoyl-2-hydroxybenzamides as Agents Active against P. falciparum (K1 strain), Trypanosomes, and Leishmania

Synthesis, Biological Evaluation, and Structure–Activity Relationships of N-Benzoyl-2-hydroxybenzamides as Agents Active against P. falciparum (K1 strain), Trypanosomes, and Leishmania

Biotechnology of siderophores in high-impact scientific fields

Recent Achievements on Siderophore Production and Application

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