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Identification of Anti‐Mycobacterial Biofilm Agents Based on the 2‐Aminoimidazole Scaffold
Author(s) -
Nguyen T. Vu,
Minrovic Bradley M.,
Melander Roberta J.,
Melander Christian
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900033
Subject(s) - biofilm , mycobacterium smegmatis , microbiology and biotechnology , mycobacterium tuberculosis , isoniazid , rifampicin , tuberculosis , multidrug tolerance , antibiotics , biology , bacteria , medicine , genetics , pathology
Tuberculosis (TB) remains a significant global health problem for which new therapeutic options are sorely needed. The ability of the causative agent, Mycobacterium tuberculosis , to reside within host macrophages and form biofilm‐like communities contributes to the persistent and drug‐tolerant nature of the disease. Compounds that can prevent or reverse the biofilm‐like phenotype have the potential to serve alongside TB antibiotics to overcome this tolerance, and decrease treatment duration. Using Mycobacterium smegmatis as a surrogate organism, we report the identification of two new 2‐aminoimidazole compounds that inhibit and disperse mycobacterial biofilms, work synergistically with isoniazid and rifampicin to eradicate preformed M. smegmatis biofilms in vitro, are nontoxic toward Galleria mellonella , and exhibit stability in mouse plasma.