| Revue: | Memorias do Instituto Oswaldo Cruz |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000459430 |
| ISSN: | 0074-0276 |
| Autores: | Rodríguez Carlos, Adrián1 Jacobo Delgado, Yolanda1 Santos Mena, Alan Orlando1 García Hernández, Mariana H1 De Jesús Gonzalez, Luis Adrián1 Lara Ramírez, Edgar E2 Rivas Santiago, Bruno1 |
| Instituciones: | 1Instituto Mexicano del Seguro Social, Unidad de Investigación Médica de Zacatecas, Zacatecas. México 2Instituto Politécnico Nacional, Centro de Biotecnología Genómica, Reynosa, Tamaulipas. México |
| Año: | 2023 |
| Volumen: | 118 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental, aplicado |
| Resumen en inglés | Tuberculosis (TB) is a major public health problem, which has been aggravated by the alarming growth of drug-resistant tuberculosis. Therefore, the development of a safer and more effective treatment is needed. OBJECTIVES The aim of this work was repositioning and evaluate histone deacetylases (HDAC) inhibitors- based drugs with potential antimycobacterial activity. METHODS Using an in silico pharmacological repositioning strategy, three molecules that bind to the catalytic site of histone deacetylase were selected. Pneumocytes type II and macrophages were infected with Mycobacterium tuberculosis and treated with pre-selected HDAC inhibitors (HDACi). Subsequently, the ability of each of these molecules to directly promote the elimination of M. tuberculosis was evaluated by colony-forming unit (CFU)/mL. We assessed the expression of antimicrobial peptides and respiratory burst using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) FINDINGS Aminoacetanilide (ACE), N-Boc-1,2-phenylenediamine (N-BOC), 1,3-Diphenylurea (DFU), reduce bacillary loads in macrophages and increase the production of β-defensin-2, LL-37, superoxide dismutase (SOD) 3 and inducible nitric oxide synthase (iNOS). While only the use of ACE in type II pneumocytes decreases the bacterial load through increasing LL-37 expression. Furthermore, the use of ACE and rifampicin inhibited the survival of intracellular multi-drug resistance M. tuberculosis. MAIN CONCLUSIONS Our data support the usefulness of in silico approaches for drug repositioning to provide a potential adjunctive therapy for TB |
| Disciplinas: | Medicina |
| Palabras clave: | Farmacología, Inmunología, Resistencia a fármacos, Tuberculosis, Inmunidad innata, Inhibidores enzimáticos, Histona deacetilasa, Mycobacterium tuberculosis |
| Keyword: | Pharmacology, Immunology, Drug resistance, Tuberculosis, Innate immunity, Enzyme inhibitors, Histone deacetylase, Mycobacterium tuberculosis |
| Texte intégral: | Texto completo (Ver HTML) Texto completo (Ver PDF) |
