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Int J Mol Sci ; 21(17)2020 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-32867307

RESUMEN

Outside of Mycobacterium tuberculosis and Mycobacterium leprae, nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.


Asunto(s)
Antibacterianos/farmacología , Proteínas de Transporte de Membrana/metabolismo , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Micobacterias no Tuberculosas/metabolismo , Antibacterianos/uso terapéutico , Proteínas Bacterianas/metabolismo , Transporte Biológico/efectos de los fármacos , Descubrimiento de Drogas , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Humanos , Yodóforos/farmacología , Yodóforos/uso terapéutico , Isoxazoles/farmacología , Isoxazoles/uso terapéutico , Infecciones por Mycobacterium no Tuberculosas/metabolismo , Ácidos Micólicos/metabolismo , Micobacterias no Tuberculosas/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Compuestos de Espiro/farmacología , Compuestos de Espiro/uso terapéutico
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