The Repurposing of FDA-Approved Drugs as FtsZ Inhibitors against Mycobacterium tuberculosis : An In Silico and In Vitro Study.

Autor:	Tovar-Nieto AM; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Interior of Alameda 45, Colonia Centro, Zacatecas 98000, Mexico., Flores-Padilla LE; Centro de Estudios Científicos y Tecnológicos 18 Zacatecas, Instituto Politécnico Nacional, Zacatecas 98160, Mexico., Rivas-Santiago B; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Interior of Alameda 45, Colonia Centro, Zacatecas 98000, Mexico., Trujillo-Paez JV; Centro de Estudios Científicos y Tecnológicos 18 Zacatecas, Instituto Politécnico Nacional, Zacatecas 98160, Mexico., Lara-Ramirez EE; Pharmaceutical Biotechnology Laboratory, Genomic Biotechnology Center, Polytechnic Institute National, Reynosa 88710, Mexico., Jacobo-Delgado YM; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Interior of Alameda 45, Colonia Centro, Zacatecas 98000, Mexico., López-Ramos JE; Centro de Estudios Científicos y Tecnológicos 18 Zacatecas, Instituto Politécnico Nacional, Zacatecas 98160, Mexico., Rodríguez-Carlos A; Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Interior of Alameda 45, Colonia Centro, Zacatecas 98000, Mexico.
Jazyk:	angličtina
Zdroj:	Microorganisms [Microorganisms] 2024 Jul 23; Vol. 12 (8). Date of Electronic Publication: 2024 Jul 23.
DOI:	10.3390/microorganisms12081505
Abstrakt:	Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis, remains one of the leading causes of death from a single infectious agent. Furthermore, the growing evolution to multi-drug-resistant (MDR) strains requires de novo identification of drug targets for evaluating candidates or repurposing drugs. Hence, targeting FtsZ, an essential cell division protein, is a promising target. Methods: Using an in silico pharmacological repositioning strategy, four FDA-based drugs that bind to the catalytic site FtsZ were selected. The Alamar Blue colorimetric assay was used to assess antimicrobial activity and the effect of drugs on Mtb growth through growth curves. Bacterial load was determined with an in vitro infection model using colony-forming units (CFU)/mL, and cytotoxicity on human monocyte-derived macrophages (MDMhs) was assessed by flow cytometry. Results: Paroxetine and nebivolol exhibited antimycobacterial activity against both reference TB and MDR strains at a concentration of 25 µg/mL. Furthermore, both paroxetine and nebivolol demonstrated a significant reduction ( p < 0.05) in viable bacteria compared to the untreated group in the in vitro infection model. Conclusions: Collectively, our findings demonstrate that the use of paroxetine and nebivolol is a promising strategy to help in the control of tuberculosis infection.
Databáze:	MEDLINE
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