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

Front Chem. 2024 Jun 26:12:1420593. doi: 10.3389/fchem.2024.1420593. eCollection 2024.

Abstract

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 Staphylococcus aureus 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 in vitro. The stability of the most active molecule, 8bE, was assessed using molecular dynamics (MD) simulation. Significantly, compound 8bE could also inhibit the S. aureus biofilm at low concentrations. Furthermore, the capability of the synthesized molecule to inhibit S. aureus biofilm formation on medical devices like urinary catheters is also demonstrated.

Keywords: Staphylococcus aureus; benzothiazine; biofilm; catheter; computational studies; peptide deformylase.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the NIPER-Kolkata AMR research fund from the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India.