Exploration of a benzothiophene scaffold for use as adjuvants with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus
Abstract
(MRSA), while over-expression of PBP4 mediates resistance to fifth-generation cephalosporins. We previously identified benzothiophene NDM-335 as an inhibitor of PBP4 that overcomes PBP4 mediated resistance to ceftobiprole, and have shown that other PBP4 inhibitor scaffolds can be tuned to overcome PBP2a-mediated resistance. Based upon this precedent, we conducted a structure activity relationship (SAR) study on the NDM-335 scaffold to uncover compounds that overcome PBP2a-mediated oxacillin resistance in MRSA, with the lead compound lowering the minimum inhibitory concentration 32-fold at 5 μM. Further development of this new adjuvant lead could potentially deliver a new combination therapy for treating MRSA infections.
Fields of Study & Subjects
Antibiotics Pharmacokinetics and Efficacy
Phenothiazines and Benzothiazines Synthesis and Activities
Synthesis of β-Lactam Compounds
Publication details
- Journal / source
- RSC Medicinal Chemistry
- Publisher
- Royal Society of Chemistry (RSC)
- Volume
- 17
- Issue
- 5
- Pages
- 2444–2454
- Publication date
- 1 January 2026
- Language
- EN