DprE1 and Ddn as promising therapeutic targets in the development of novel anti-tuberculosis nitroaromatic drugs.
Eur J Med Chem
; 274: 116559, 2024 Aug 05.
Article
en En
| MEDLINE
| ID: mdl-38850856
ABSTRACT
Tuberculosis remains the second deadliest infectious disease in humans and a public health threat due to the emergence of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. Therefore, it is urgent to identify new anti-tuberculosis treatments and novel therapeutic targets to prevent the emergence of resistance. In recent years, the study of anti-tuberculosis properties of nitroaromatic compounds has led to the identification of two novel biological targets, the deazaflavin (F420)-dependent nitroreductase Ddn and the decaprenylphosphoryl-ß-d-ribose 2'-epimerase DprE1. This review aims to show why Ddn and DprE1 are promising therapeutic targets and highlight nitroaromatic compounds interest in developing new anti-tuberculosis treatments active against MDR-TB and XDR-TB. Despite renewed interest in the development of new anti-tuberculosis nitroaromatic compounds, pharmaceutical companies often exclude nitro-containing molecules from their drug discovery programs because of their toxic and mutagenic potential. This exclusion results in missed opportunities to identify new nitroaromatic compounds and promising therapeutic targets.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nitrorreductasas
/
Mycobacterium tuberculosis
/
Antituberculosos
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Francia