Design and Synthesis of Sulfanilamide Aminophosphonates as Novel Antibacterial Agents towards Escherichia coli

Main observation and conclusion The limit ability of traditional antibiotics to treat drug resistant bacteria calls for new therapeutic alternatives. A class of unique sulfanilamide aminophosphonates as new potential agents against microbes was synthesized by one-pot three-component reaction. Noticeably, fluorobenzyl derivative 5d (MIC = 2 mu g/mL) was active against drug resistant E. coli infection and exerted no obvious toxicity towards human mammalian cells. Compound 5d also displayed good anti-biofilm activity and low possibility to induce drug resistance. Mechanism investigation elucidated that molecule 5d could disrupt E. coli membrane through generation of reactive oxygen (ROS) and then intercalate into deoxyribonucleic acid (DNA) to form a steady 5d-DNA complex, which led to bacterial death. These results indicated that sulfanilamide aminophosphonates would shed light on developing novel potential antibacterial agents.

Automated summary

A new class of sulfanilamide aminophosphonates showed activity against drug resistant bacteria and low toxicity to human cells, indicating potential as novel antibacterial agents. Mechanistic studies revealed that the compound disrupted bacterial cell membrane and formed a stable complex leading to bacterial death.