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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.
Affiliation
  • Rodríguez-Carlos, Adrián; Medical Research Unit-Zacatecas. Mexican Institute for Social Security-IMSS. Zacatecas. MX
  • Jacobo-Delgado, Yolanda; Medical Research Unit-Zacatecas. Mexican Institute for Social Security-IMSS. Zacatecas. MX
  • Santos-Mena, Alan Orlando; Medical Research Unit-Zacatecas. Mexican Institute for Social Security-IMSS. Zacatecas. MX
  • García-Hernández, Mariana H; Medical Research Unit-Zacatecas. Mexican Institute for Social Security-IMSS. Zacatecas. MX
  • De Jesus-Gonzalez, Luis Adrian; Medical Research Unit-Zacatecas. Mexican Institute for Social Security-IMSS. Zacatecas. MX
  • Lara-Ramirez, Edgar E; Instituto Politécnico Nacional. Centro de Biotecnología Genómica. Laboratorio de Biotecnología Farmacéutica. Reynosa. MX
  • Rivas-Santiago, Bruno; Medical Research Unit-Zacatecas. Mexican Institute for Social Security-IMSS. Zacatecas. MX
Mem. Inst. Oswaldo Cruz ; 118: e230143, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1529018
Responsible library: BR1.1
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 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.


Full text: Available Collection: International databases Health context: Sustainable Health Agenda for the Americas / SDG3 - Health and Well-Being / Neglected Diseases Health problem: Goal 10: Communicable diseases / Target 3.3: End transmission of communicable diseases / Neglected Diseases / Tuberculosis Database: LILACS Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2023 Document type: Article Affiliation country: Mexico Institution/Affiliation country: Instituto Politécnico Nacional/MX / Medical Research Unit-Zacatecas/MX

Full text: Available Collection: International databases Health context: Sustainable Health Agenda for the Americas / SDG3 - Health and Well-Being / Neglected Diseases Health problem: Goal 10: Communicable diseases / Target 3.3: End transmission of communicable diseases / Neglected Diseases / Tuberculosis Database: LILACS Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2023 Document type: Article Affiliation country: Mexico Institution/Affiliation country: Instituto Politécnico Nacional/MX / Medical Research Unit-Zacatecas/MX
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