Design,synthesis and biological evaluation of amino organophosphorus imidazoles as a new type of potential antimicrobial agents

作     者：Wei-Wei Gao Syed Rasheed VijaiKumarReddy Tangadanchu Yi Sun Xin-Mei Peng Yu Cheng Feng-Xiu Zhang Jian-Mei Lin Cheng-He Zhou 

作者机构：Institute of Bioorganic&Medicinal ChemistryKey Laboratory of Applied Chemistry of Chongqing MunicipalitySchool of Chemistry and Chemical EngineeringSouthwest UniversityChongqing 400715China School of Medicine University of Electronic Science and Technology of ChinaChengdu 610072China 

基　　金：supported by the National Natural Science Foundation of China(21672173,21372186) Research Fund for International Young Scientists from International(Regional)Cooperation and Exchange Program(81350110523) Chongqing Special Foundation for Postdoctoral Research Proposal(Xm2014127,Xm2016039) Fundamental Research Funds for the Central Universities(XDJK2016E059) 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2017年第60卷第6期

页      码：769-785页

摘      要：A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial *** evaluation in vitro showed that compound 3f exhibited equipotent or superior anti-methicillin-resistant Staphylococcus aureus(anti-MRSA) and anti-S. cerevisiae efficiencies(minimal inhibitory concentration(MIC)=2 μg/mL) to clinical drugs,and the combinations with antibacterial or antifungal drugs enhanced the antimicrobial efficiency. Highly active molecule 3f showed low propensity for bacteria to develop resistance, and the preliminary action mechanism studies demonstrated that 3f was membrane-active, but had no significant intercalation towards MRSA DNA. The computational study on 3f reasonably explained its high antimicrobial activity. Experimental data revealed that ground-state 3f-HSA complexes were formed mainly through hydrophobic interactions and hydrogen bonds with a spontaneous process, and the non-radioactive energy transfer from HSA to 3f occurred beyond F鰎ster resonance energy transfer theory. The participation of metal ions in 3f-HSA supramolucular system could increase the concentration of free compound 3f, and shorten its storage time and half-life in the blood to improve the maximum antimicrobial efficacy.

主 题 词：organophosphorus imidazole antibacterial antifungal HSA 

学科分类：1007[医学-药学类] 100705[100705] 0703[理学-化学类] 10[医学] 

核心收录：

D　O　I：10.1007/s11426-016.9009-6

馆 藏 号：203140927...