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Biomolecules

Biomolecules

IF: 4.8
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Repurposing an Antioxidant to Kill Mycobacterium tuberculosis by Targeting the 50S Subunit of the Ribosome

Published:14 December 2023 DOI: 10.3390/biom13121793
Wenqi Dong, Gaoyan Wang, Yajuan Bai, Yuxin Li, Liying Zhao, Wenjia Lu, Chenchen Wang, Zhaoran Zhang, Hao Lu, Xiangru Wang, Huanchun Chen, Chen Tan

Abstract

Tuberculosis and drug-resistant TB remain serious threats to global public health. It is urgent to develop novel anti-TB drugs in order to control it. In addition to redesigning and developing new anti-TB drugs, drug repurposing is also an innovative way to develop antibacterial drugs. Based on this method, we discovered SKQ-1 in the FDA-approved drug library and evaluated its anti-TB activity. In vitro, we demonstrated that SKQ-1 engaged in bactericidal activity against drug-sensitive and -resistant Mtb and confirmed the synergistic effects of SKQ1 with RIF and INH. Moreover, SKQ-1 showed a significant Mtb-killing effect in macrophages. In vivo, both the SKQ-1 treatment alone and the treatment in combination with RIF were able to significantly reduce the bacterial load and improve the survival rate of G. mellonella infected with Mtb. We performed whole-genome sequencing on screened SKQ-1-resistant strains and found that the SNP sites were concentrated in the 50S ribosomal subunit of Mtb. Furthermore, we proved that SKQ-1 can inhibit protein translation. In summary, from the perspective of drug repurposing, we discovered and determined the anti-tuberculosis effect of SKQ-1, revealed its synergistic effects with RIF and INH, and demonstrated its mechanism of action through targeting ribosomes and disrupting protein synthesis, thus making it a potential treatment option for DR-TB.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
TMC-207 843663-66-1 C32H31BrN2O2 273 suppliers $40.00-$2400.00
TMC-207 843663-66-1 C32H31BrN2O2 273 suppliers $40.00-$2400.00
TMC-207 843663-66-1 C32H31BrN2O2 273 suppliers $40.00-$2400.00
TMC-207 843663-66-1 C32H31BrN2O2 273 suppliers $40.00-$2400.00
SKQ1 Bromide 934826-68-3 C36H42BrO2P 99 suppliers $31.00-$1700.00
SKQ1 Bromide 934826-68-3 C36H42BrO2P 99 suppliers $31.00-$1700.00
SKQ1 Bromide 934826-68-3 C36H42BrO2P 99 suppliers $31.00-$1700.00
SKQ1 Bromide 934826-68-3 C36H42BrO2P 99 suppliers $31.00-$1700.00

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