AUTHOR=Naithani Kaushal , Das Arka , Ushare Mamta , Nath Subham , Biswas Rashmita , Kundu Anirban , Ahmed Kazi Tawsif , Mohan Utpal , Bhowmik Subhendu 

TITLE=Design, synthesis, and evaluation of 1,4-benzothiazine-3-one containing bisamide derivatives as dual inhibitors of Staphylococcus aureus with plausible application in a urinary catheter

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1420593

DOI=10.3389/fchem.2024.1420593

ISSN=2296-2646

ABSTRACT=<p>In this study, 1,4-benzothiazine-based bisamide derivatives, a new class of antibacterial agents targeting bacterial peptide deformylase (PDF), were designed and synthesized to combat <italic>Staphylococcus aureus</italic> infection. Molecular modeling of the designed molecules showed better docking scores compared to the natural product actinonin. Bioactivity assessment identified two derivatives with promising antibacterial activity <italic>in vitro</italic>. The stability of the most active molecule, <bold>8bE</bold>, was assessed using molecular dynamics (MD) simulation. Significantly, compound <bold>8bE</bold> could also inhibit the <italic>S. aureus</italic> biofilm at low concentrations. Furthermore, the capability of the synthesized molecule to inhibit <italic>S. aureus</italic> biofilm formation on medical devices like urinary catheters is also demonstrated.</p>