Studies on the antimicrobial properties of N-acylated ciprofloxacins
摘要:
Fluoroquinolone antibiotics have been a mainstay in the treatment of bacterial diseases. The most notable representative, ciprofloxacin, possesses potent antimicrobial activity; however, a rise in resistance to this agent necessitates development of novel derivatives to prolong the clinical lifespan of these antibiotics. Herein we have synthesized and analyzed the antimicrobial properties of a library of N-acylated ciprofloxacin analogues. We find that these compounds are broadly effective against Gram-positive and Gram-negative bacteria, with many proving more effective than the parental drug, and several possessing MICs <= 1.0 mu g/ml against methicillin-resistant Staphylococcus aureus and Bartonella species. An analysis of spontaneous mutation frequencies reveals very low potential for resistance in MRSA compared to existing fluoroquinolones. Mode of action profiling reveals that modification of the piperazinyl nitrogen by acylation does not alter the effect of these molecules towards their bacterial target. We also present evidence that these N-acylated compounds are highly effective at killing intracellular bacteria, suggesting the suitability of these antibiotics for therapeutic treatment. (c) 2012 Published by Elsevier
Fluoroquinolones and use thereof to treat bacterial infections
申请人:UNIVERSITÉ PIERRE ET MARIE CURIE—PARIS 6 (UPMC)
公开号:US10087165B2
公开(公告)日:2018-10-02
The present invention relates to novel fluoroquinolones, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.
7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: Synthesis and in vitro biological evaluation as potential antitumor agents
作者:Joëlle Azéma、Brigitte Guidetti、Janique Dewelle、Benjamin Le Calve、Tatjana Mijatovic、Alexander Korolyov、Julie Vaysse、Myriam Malet-Martino、Robert Martino、Robert Kiss
DOI:10.1016/j.bmc.2009.06.053
日期:2009.8
Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC50 values ranging from mu M to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC50 values were <= 10 mu M in three (derivative 2) or four (derivative 6h) cancer cell lines. (C) 2009 Elsevier Ltd. All rights reserved.
NOVEL FLUOROQUINOLONES AND USE THEREOF TO TREAT BACTERIAL INFECTIONS
申请人:Université Pierre et Marie Curie -
Paris 6 (UPMC)
公开号:EP3157911A1
公开(公告)日:2017-04-26
[EN] NOVEL FLUOROQUINOLONES AND USE THEREOF TO TREAT BACTERIAL INFECTIONS<br/>[FR] NOUVEAUX FLUOROQUINOLONES ET LEUR UTILISATION POUR TRAITER DES INFECTIONS BACTÉRIENNES
申请人:UNIVERSITÉ PIERRE ET MARIE CURIE PARIS 6 UPMC
公开号:WO2015193454A1
公开(公告)日:2015-12-23
The present invention relates to novel fluoroquinolones, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.