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Histone deacetylase (HDAC) inhibitors- based drugs are effective to control Mycobacterium tuberculosis infection and promote the sensibility for rifampicin in MDR strain.
Rodríguez-Carlos, Adrián; Jacobo-Delgado, Yolanda; Santos-Mena, Alan Orlando; García-Hernández, Mariana H; De Jesus-Gonzalez, Luis Adrian; Lara-Ramirez, Edgar E; Rivas-Santiago, Bruno.
Afiliação
  • Rodríguez-Carlos A; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
  • Jacobo-Delgado Y; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
  • Santos-Mena AO; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
  • García-Hernández MH; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
  • De Jesus-Gonzalez LA; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
  • Lara-Ramirez EE; Instituto Politécnico Nacional, Centro de Biotecnología Genómica, Laboratorio de Biotecnología Farmacéutica, Reynosa, Mexico.
  • Rivas-Santiago B; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Mem Inst Oswaldo Cruz ; 118: e230143, 2023.
Article em En | MEDLINE | ID: mdl-38126492
ABSTRACT

BACKGROUND:

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 ß-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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Tuberculose Resistente a Múltiplos Medicamentos / Mycobacterium tuberculosis Limite: Humans Idioma: En Revista: Mem Inst Oswaldo Cruz Ano de publicação: 2023 Tipo de documento: Article País de afiliação: México País de publicação: Brasil
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Tuberculose Resistente a Múltiplos Medicamentos / Mycobacterium tuberculosis Limite: Humans Idioma: En Revista: Mem Inst Oswaldo Cruz Ano de publicação: 2023 Tipo de documento: Article País de afiliação: México País de publicação: Brasil