Novel fluorobenzothiazole as a dual inhibitor of gyrase B and topoisomerase IV against Gram-positive pathogens - Figure supplementary 3S
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posted on 2023-08-04, 14:49 authored by Tarani K Barman, Manoj KumarManoj Kumar, Tridib Chaira, Smita Singhal, Tarun Mathur, Vandana Kalia, Ramkumar Gangadharan, Madhvi Rao, Manisha Pandya, Pragya Bhateja, Ruchi Sood, Dilip J Upadhyay, Shibu Varughese, Ajay Yadav, Lalima Sharma, Venkataramanan Ramadass, Naresh Kumar, Jitendra Sattigeri, Pradip K Bhatnagar, V Samuel Raj<p> </p>
<p><strong>Aim: </strong>The development of a novel inhibitor targeting gyrase B and topoisomerase IV offers an opportunity to combat multidrug resistance. <strong>Methods: </strong>We investigated the activity of RBx 10080758 against Grampositive bacteria <em>in vitro </em>and <em>in vivo</em>. <strong>Results: </strong>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 wholecell <em>in vitro </em>activity with MIC ranges of 0.015–0.06 and 0.015–0.03 μg<strong>/</strong>ml against <em>Staphylococcus aureus </em>and <em>Streptococcus pneumoniae</em>, respectively. In a rat thigh infection model with methicillin-resistant <em>S. aureus</em>, RBx 10080758 at 45 mg<strong>/</strong>kg exhibited a <strong>></strong>3 log10 CFU reduction in thigh muscles. <strong>Conclusion: </strong>RBx 10080758 displayed potent activity against multiple multidrug-resistant Gram-positive bacteria with a dual-targeting mechanism of action. </p>
