2-Difluoromethylpyridine as a bioisosteric replacement of pyridine-N-oxide: the case of quorum sensing inhibitors.

ABSTRACT: Herein, we demonstrate that 2-difluoromethylpyridine is a bioisosteric replacement of pyridine-N-oxide. Using the quorum sensing inhibitor 4NPO as a model compound, a library of 2-difluoromethylpyridine derivatives was designed, synthesized, and evaluated toward quorum sensing activity, biofilm formation, anti-violacein activity, and protease activity. As a result, compounds 1 (IC₅₀ of 35 ± 1.12 μM), 5 (IC₅₀ of 19 ± 1.01 μM), and 6 (IC₅₀ of 27 ± 0.67 μM) showed a similar or better activity in comparison to 4NPO (IC₅₀ of 33 ± 1.12 μM) in a quorum sensing system of Pseudomonas aeruginosa. In addition, compounds 1, 5, 6, and 4NPO showed good antibiofilm biomass of Pseudomonas aeruginosa and reduced violacein

SUBMITTER: Tung TT 

PROVIDER: S-EPMC8672814 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature