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Future Med Chem ; 11(13): 1565-1582, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31469336

RESUMO

Aim:Stenotrophomonas maltophilia (Sm) and Burkholderia cepacia complex (BCC) are Gram-negative bacterial pathogens, which are typically multidrug resistant and excellent biofilm producers. These phenotypes are controlled by quorum sensing (QS) systems from the diffusible signal factor (DSF) family. We aim to interfere with this QS system as an alternative approach in combatting such difficult-to-treat infections. Materials & methods: A library of sulfonamide-based DSF bioisosteres was synthesized and tested against the major phenotypes regulated by QS. Results & conclusion: Several analogs display significant antibiofilm activity while the majority increase the action of the last-resort antibiotic colistin against Sm and BCC. Most compounds inhibit DSF synthesis in the Sm K279a strain. Our results support the strategy of interfering with QS communications to combat multidrug resistance.


Assuntos
Antibacterianos/farmacologia , Burkholderia cepacia/efeitos dos fármacos , Stenotrophomonas maltophilia/efeitos dos fármacos , Sulfonamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Cinética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Percepção de Quorum/efeitos dos fármacos , Sulfonamidas/síntese química , Sulfonamidas/química
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