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Future Med Chem ; 11(13): 1565-1582, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31469336

RESUMEN

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.


Asunto(s)
Antibacterianos/farmacología , Burkholderia cepacia/efectos de los fármacos , Stenotrophomonas maltophilia/efectos de los fármacos , Sulfonamidas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Biopelículas/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Cinética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Percepción de Quorum/efectos de los fármacos , Sulfonamidas/síntesis química , Sulfonamidas/química
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