In vitro and Intracellular Antibacterial Activity of Sudapyridine (WX-081) Against Tuberculosis

Sudapyridine (WX-081) has exhibited equivalent efficacy than its counterpart parent drug bedaquiline (BDQ) but better safety profile against Mycobacterium tuberculosis (Mtb). Our study was aimed to evaluate in vitro activity of WX-081 against the clinical isolates of Mtb with different drug-resistance profiles and the intracellular bactericidal activity against the reference strain.

The minimum inhibitory concentrations (MICs) of WX-081 and BDQ were tested against 114 Mtb clinical isolates. The intracellular activity of WX-081 and BDQ against the Mtb reference strain H37Rv in THP-1 cells was also evaluated in parallel.

The MICs for WX-081 of the enrolled isolates ranged from 0.0156 μg/mL to 1 μg/mL. The MIC₅₀ and MIC₉₀ of WX-081 were, respectively, 0.25 μg/mL and 0.5 μg/mL, with 95.6% of the enrolled strains having MICs ≤0.25 μg/mL. For a given strain, the MIC value of WX-081 was generally equivalent to or 2-fold than MIC of BDQ. The intracellular bacterial killing was acquired with the tested drug concentrations that were presumed attainable during clinical usage.

WX-081 exhibited potent efficacy against the clinical isolates in vitro. The intracellular killing effect of sudapyridine against the reference strain supports its potential efficacy in treating TB patients.