biostudies-literatureUnknown12(12)Tung TTHerein, 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 violaceinRSC medicinal chemistry2065-2070https://www.ebi.ac.uk/biostudies/studies/S-EPMC8672814biostudies-literature2-Difluoromethylpyridine as a bioisosteric replacement of pyridine-N-oxide: the case of quorum sensing inhibitors.PMC8672814Nguyen Quoc TTung TTfalse2-Difluoromethylpyridine as a bioisosteric replacement of pyridine-N-oxide: the case of quorum sensing inhibitors.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 violacein2021-01-01T00:00:00Z2021 Dec2026-05-08T11:35:42.82Z2024-11-07T03:41:13.846ZS-EPMC86728143502856510.1039/d1md00245g