1. Novel fluorobenzothiazole as a dual inhibitor of gyrase B and topoisomerase IV against Gram-positive pathogens.
- Author
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Barman TK, Kumar M, Chaira T, Singhal S, Mathur T, Kalia V, Gangadharan R, Rao M, Pandya M, Bhateja P, Sood R, Upadhyay DJ, Varughese S, Yadav A, Sharma L, Ramadass V, Kumar N, Sattigeri J, Bhatnagar PK, and Raj VS
- Subjects
- Rats, Animals, Anti-Bacterial Agents pharmacology, Topoisomerase II Inhibitors pharmacology, Microbial Sensitivity Tests, DNA Topoisomerase IV, Methicillin-Resistant Staphylococcus aureus
- Abstract
Aim: The development of a novel inhibitor targeting gyrase B and topoisomerase IV offers an opportunity to combat multidrug resistance. Methods: We investigated the activity of RBx 10080758 against Gram-positive bacteria in vitro and in vivo . Results: RBx 10080758 showed a potent 50% inhibitory concentration of 0.13 μM and 0.25 μM against gyrase B and topoisomerase IV, respectively, and exhibited strong whole-cell in vitro activity with MIC ranges of 0.015-0.06 and 0.015-0.03 μg/ml against Staphylococcus aureus and Streptococcus pneumoniae , respectively. In a rat thigh infection model with methicillin-resistant S. aureus , RBx 10080758 at 45 mg/kg exhibited a >3 log
10 CFU reduction in thigh muscles. Conclusion: RBx 10080758 displayed potent activity against multiple multidrug-resistant Gram-positive bacteria with a dual-targeting mechanism of action.- Published
- 2023
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