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Synthesis and Activity of Biomimetic Biofilm Disruptors

2013; American Chemical Society; Volume: 135; Issue: 8 Linguagem: Inglês

10.1021/ja3120955

1943-2984

Thomas Böttcher, Ilana Kolodkin–Gal, Roberto Kolter, Richard Losick, Jon Clardy,

bioluminescence and chemiluminescence research

Biofilms are often associated with human bacterial infections, and the natural tolerance of biofilms to antibiotics challenges treatment. Compounds with antibiofilm activity could become useful adjuncts to antibiotic therapy. We used norspermidine, a natural trigger for biofilm disassembly in the developmental cycle of Bacillus subtilis, to develop guanidine and biguanide compounds with up to 20-fold increased potency in preventing biofilm formation and breaking down existing biofilms. These compounds also were active against pathogenic Staphylococcus aureus. An integrated approach involving structure–activity relationships, protonation constants, and crystal structure data on a focused synthetic library revealed that precise spacing of positively charged groups and the total charge at physiological pH distinguish potent biofilm inhibitors.