Authors
Mine Buga Aktekin, Zehra Oksuz, Mehmet Abdullah Alagoz, Bahar Uluca Han, Oztekin Algul
Published in
Future medicinal chemistry. Pages 1-19. Aug 10, 2026. Epub Aug 10, 2026.
Abstract
Antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), have renewed interest in antivirulence strategies. This study aimed to design, synthesize, and evaluate asymmetric di‑heterocyclic benzazole derivatives as antibiofilm agents targeting wall teichoic acid (WTA) biosynthesis.
Twenty‑one novel bis‑heterocyclic benzazole derivatives bearing an ethyl‑thio linker were synthesized and characterized. Antibacterial activity was determined by broth microdilution. Antibiofilm activity (inhibition and eradication) was assessed at sub‑minimal inhibitory concentrations (sub‑MICs) using crystal violet. Molecular docking and 200 ns molecular dynamics (MD) simulations were performed against key WTA enzymes (TarGH, TarS, TarM, TarL, and TarJ).
Compounds 18, 21, 23, and 24 showed potent antibacterial activity against methicillin‑susceptible S. aureus (MSSA) and MRSA, with MIC values as low as 15.62 µg/mL. All selected compounds significantly inhibited biofilm at sub‑MIC levels. Compound 24 was most effective, with an MBIC50 of 3.90 µg/mL against MSSA and eradicated pre‑formed biofilms at 7.81 µg/mL. Docking and MD simulations revealed stable interactions of compounds 23 and 24 with TarGH and TarS, suggesting a WTA‑targeting mechanism.
Di‑heterocyclic benzazole derivatives, especially compound 24, are promising scaffolds for antibiofilm agents against S. aureus. Our findings support further mechanistic and preclinical evaluation as potential antivirulence therapeutics.
PMID:
42572864
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.
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