首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Synthesis and biological evaluation of aryl phosphoramidate prodrugs of fosfoxacin and its derivatives
Institution:1. Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA;2. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA;3. Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA;4. Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA;1. University of Florence, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;2. University of Pisa, Department of Pharmacy, Via Bonanno 6, 56126 Pisa, Italy;3. University of Florence, NEUROFARBA Dept., Sezione di Farmacologia e Tossicologia, Viale Gaetano Pieraccini 6, 50139 Florence, Italy;4. Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, ENSCM, Université de Montpellier, 240 avenue du Professeur Emile Jeanbrau, 34296 Montpellier Cedex 05, France;1. Department of Organic Chemistry, Faculty of Chemistry, University of Seville, C/Prof. García González, 1, 41012 Seville, Spain;2. Department of Crystallography and Structural Biology, Institute of Physical-Chemistry Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain;3. Institute of Agricultural Chemistry and Food Technology, CSIC, 46980 Paterna, Valencia, Spain;4. Department of Chemistry ‘Ugo Schiff’, University of Firenze, via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy;1. Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849-5312, United States;2. Department of Chemistry, Slippery Rock University, Slippery Rock, PA 16057, United States;3. Microbiotix, Inc., Worcester, MA 01605, United States;1. The NeaNat Group, Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano 49, 80131 Napoli, Italy;2. Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università di Milano, Via Pascal 36, 20133 Milan, Italy;3. Istituto di Chimica del Riconoscimento Molecolare, CNR, Via M. Bianco 9, 20131 Milano, Italy;1. Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, 09972-270 São Paulo, Brazil;2. Center of Natural Sciences and Humanities, Universidade Federal do ABC, 09210-580 Santo Andre, São Paulo, Brazil;3. Centre for Parasitology and Mycology, Instituto Adolfo Lutz, 01246-000 São Paulo, SP, Brazil
Abstract:Aryl phosphoramidate prodrugs of fosfoxacin derivatives 15a-b and 8a-b were synthesized and investigated for their ability to target bacteria. No growth inhibition was observed neither for Mycobacterium smegmatis nor for Escherichia coli on solid medium, demonstrating the absence of release of the active compounds in the bacterial cells. Investigation of the stability of the prodrugs and their multienzymatic cleavage in abiotic and biotic conditions showed that the use of aryl phosphoramidate prodrug approach to deliver non-nucleotides compounds is not obvious and might not be appropriate for an antimicrobial drug.
Keywords:Phosphate prodrug  Antimicrobials  MEP pathway  DXR  DXP"}  {"#name":"keyword"  "$":{"id":"k0035"}  "$$":[{"#name":"text"  "$$":[{"#name":"__text__"  "_":"1-deoxy-"}  {"#name":"small-caps"  "_":"d"}  {"#name":"__text__"  "_":"-xylulose 5-phosphate  DXR"}  {"#name":"keyword"  "$":{"id":"k0045"}  "$$":[{"#name":"text"  "$$":[{"#name":"__text__"  "_":"1-deoxy-"}  {"#name":"small-caps"  "_":"d"}  {"#name":"__text__"  "_":"-xylulose 5-phosphate reductoisomerase  MEP"}  {"#name":"keyword"  "$":{"id":"k0055"}  "$$":[{"#name":"text"  "$$":[{"#name":"__text__"  "_":"2-"}  {"#name":"italic"  "_":"C"}  {"#name":"__text__"  "_":"-methyl-"}  {"#name":"small-caps"  "_":"d"}  {"#name":"__text__"  "_":"-erythritol 4-phosphate  CPY"}  {"#name":"keyword"  "$":{"id":"k0065"}  "$$":[{"#name":"text"  "_":"carboxypeptidase Y  GlpT"}  {"#name":"keyword"  "$":{"id":"k0075"}  "$$":[{"#name":"text"  "_":"glycerol 3-phosphate transporter
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号