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

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Abstract

A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial agents. Bioactive 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 Förster 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.

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Acknowledgments

This work was partially 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), and Fundamental Research Funds for the Central Universities (XDJK2016E059).

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Authors and Affiliations

  1. Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China

    Wei-Wei Gao, Syed Rasheed, VijaiKumarReddy Tangadanchu, Yi Sun, Xin-Mei Peng, Yu Cheng, Feng-Xiu Zhang & Cheng-He Zhou

  2. School of Medicine University of Electronic Science and Technology of China, Chengdu, 610072, China

    Jian-Mei Lin

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  1. Wei-Wei Gao
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Correspondence to Jian-Mei Lin or Cheng-He Zhou.

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11426_2016_9009_MOESM1_ESM.pdf

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

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Gao, WW., Rasheed, S., Tangadanchu, V. et al. Design, synthesis and biological evaluation of amino organophosphorus imidazoles as a new type of potential antimicrobial agents. Sci. China Chem. 60, 769–785 (2017). https://doi.org/10.1007/s11426-016-9009-6

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  • DOI: https://doi.org/10.1007/s11426-016-9009-6

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