Cyclophostin and Cyclipostins analogues, new promising molecules to treat mycobacterial-related diseases.
Int J Antimicrob Agents
; 51(4): 651-654, 2018 Apr.
Article
en En
| MEDLINE
| ID: mdl-29241819
ABSTRACT
The progression of mycobacterial diseases requires the development of new therapeutics. This study evaluated the efficacy and selectivity of a panel of Cyclophostin and Cyclipostins analogues (CyCs) against various bacteria and mycobacteria. The activity 26 CyCs was first assayed by the agar plate method. Compounds exhibiting 50-100% growth inhibition were then selected to determine their minimum inhibitory concentrations (MICs) by the resazurin microtiter assay (REMA). The best drug candidate was further tested against clinical mycobacterial isolates and bacteria responsible for nosocomial infections, including 6 Gram-negative bacteria, 5 Gram-positive bacteria, 29 rapid-growing mycobacteria belonging to the Mycobacterium chelonae-abscessus clade and 3 slow-growing mycobacteria (Mycobacterium marinum, Mycobacterium bovis BCG and Mycobacterium tuberculosis). Among the 26 CyCs tested, 10 were active and their inhibitory activity was exclusively restricted to mycobacteria. The best candidate (CyC17) was further tested against 26 clinical strains and showed high selectivity for mycobacteria, with MICs (<2-40 µg/mL) comparable with those of most classical antimicrobials used to treat M. abscessus infections. Together, these results support the fact that such CyCs represent a new family of potent and selective inhibitors against mycobacteria. This is of particular interest for future chemotherapeutic developments against mycobacterial-associated infections, especially against M. abscessus, the most drug-resistant mycobacterial species.
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Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Plantas_medicinales
Asunto principal:
Compuestos Organofosforados
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Mycobacterium marinum
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Mycobacterium abscessus
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Antibacterianos
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Mycobacterium bovis
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Infecciones por Mycobacterium
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Mycobacterium tuberculosis
Idioma:
En
Revista:
Int J Antimicrob Agents
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia