BWC0977

BWC0977 is an effective topoisomerase inhibitor that disrupts bacterial DNA replication by targeting both DNA gyrase and topoisomerase IV. BWC0977 exhibits a minimum inhibitory concentration (MIC90) against multidrug-resistant Gram-negative bacteria ranging from 0.03 to 2 µg/mL. BWC0977 is therefore applied in antibacterial pharmacology research to investigate dual topoisomerase inhibition mechanisms and resistance profiles in Gram-negative bacterial model systems.

Methods:The MIC₅₀ values of BWC0977 against multiple standard strains were determined. Its bactericidal kinetics, in vitro spontaneous resistance frequency and cross-resistance profiles were evaluated.
Results:
1.BWC0977 exhibited potent antibacterial activity against various ATCC standard strains. The median MIC₅₀ was 0.01 μg/mL for Staphylococcus aureus, 0.06 μg/mL for Enterococcus faecalis, 0.03 μg/mL for both Escherichia coli and Klebsiella pneumoniae, 0.25 μg/mL for Pseudomonas aeruginosa, 0.06 μg/mL for both Acinetobacter baumannii and Enterobacter cloacae, and 0.12 μg/mL for Proteus mirabilis.
2.At concentrations of 0.008–256 μg/mL over 0–24 hours, BWC0977 exerted time-dependent bactericidal effects on susceptible strains and multidrug-resistant (MDR) strains of E. coli, A. baumannii, K. pneumoniae, P. aeruginosa and E. cloacae .
3.When treated at 4×MIC for 24–36 hours, BWC0977 showed low in vitro spontaneous resistance frequency against the above ATCC strains and MDR strains. No cross-resistance was found between resistant clones and other antibiotics [1].

Methods:Neutropenic mouse thigh infection model and rat pulmonary infection model were established respectively. Animals were treated with BWC0977 at different doses, administration routes and frequencies. The in vivo antibacterial efficacy was evaluated and pharmacodynamic drivers were analyzed.
Results:
1.In the mouse thigh infection model, subcutaneous administration of BWC0977 at 40–160 mg/kg every 6–24 hours for 26 consecutive days produced bactericidal effects in a dose-dependent manner. The ED₅₀ was 58 mg/kg q8h, and fAUC/MIC served as the major pharmacodynamic driver.
2.In the rat pulmonary infection model, intravenous infusion of BWC0977 at 160–450 mg/kg for 2 hours with dosing every 8–24 hours within 24 hours exerted potent bactericidal activity against multidrug-resistant Gram-negative bacteria. Its efficacy was also primarily driven by fAUC/MIC.