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

将 FDA 批准的药物重新用作抗结核分枝杆菌的 FtsZ 抑制剂:一项计算机模拟和体外研究

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作者:Andrea Michel Tovar-Nieto, Luis Enrique Flores-Padilla, Bruno Rivas-Santiago, Juan Valentin Trujillo-Paez, Edgar Eduardo Lara-Ramirez, Yolanda M Jacobo-Delgado, Juan Ernesto López-Ramos, Adrián Rodríguez-Carlos

Conclusions

Collectively, our findings demonstrate that the use of paroxetine and nebivolol is a promising strategy to help in the control of tuberculosis infection.

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.

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