2026-10-19T00:27:45Zhttps://ebyu-rdlopen.rawdatalibrary.net/oai/request

oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/106792026-10-18T21:13:06Zopenairedrivercom_ebyu_10000col_ebyu_10001

Asymmetric benzazole derivatives as dual antibiofilm and anti-wall teichoic acid agents against Staphylococcus aureusBuga Aktekin, MineOksuz, ZehraAlagoz, Mehmet AbdullahUluca Han, BaharAlgul, OztekinantibiofilmantivirulenceBenzazoleStaphylococcus aureusteichoic acidsAnti-Bacterial AgentsAzolesBiofilmsCell WallMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsMolecular Docking SimulationMolecular Dynamics SimulationMolecular StructureStructure-Activity Relationship2 [2 [(1h benzo[d]imidazol 2 yl)thio]ethyl] 5 bromo 1h benzo[d]imidazole derivative2 [2 [(1h benzo[d]imidazol 2 yl)thio]ethyl] 5 chloro 1h benzo[d]imidazole derivative2 [2 [(1h benzo[d]imidazol 2 yl)thio]ethyl] 5 fluoro 1h benzo[d]imidazole derivative2 [2 [(1h benzo[d]imidazol 2 yl)thio]ethyl] 5 methyl 1h benzo[d]imidazole derivative2 [2 [(1h benzo[d]imidazol 2 yl)thio]ethyl] 5 nitro 1h benzo[d]imidazole derivative2 [2 [(1h benzo[d]imidazol 2 yl)thio]ethyl] 5,6 dichloro 1h benzo[d]imidazole derivative2 [[2 (1h benzo[d]imidazol 2 yl)ethyl]thio] 1h benzo[ d]imidazole derivative2 [[2 (1h benzo[d]imidazol 2 yl)ethyl]thio] benzo[d] oxazole derivative2 [[2 (1h benzo[d]imidazol 2 yl)ethyl]thio] benzo[d] thiazole derivative2 [[2 (5 bromo 1h benzo[d]imidazol 2 yl)ethyl] thio]benzo[d]thiazole derivative2 [[2 (5 bromo 1h benzo[d]imidazol 2 yl)ethyl]thio]benzo[d]oxazole derivative2 [[2 (5 chloro 1h benzo[d]imidazol 2 yl)ethyl]thio] benzo[d]oxazole derivative2 [[2 (5 chloro 1h benzo[d]imidazol 2 yl)ethyl]thio] benzo[d]thiazole derivative2 [[2 (5 fluoro 1h benzo[d]imidazol 2 yl)ethyl]thio] benzo[d]oxazole derivative2 [[2 (5 fluoro 1h benzo[d]imidazol 2 yl)ethyl]thio] benzo[d]thiazole derivativeAims: 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. Materials and methods: 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). Results: 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. Conclusions: 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. © 2026 Informa UK Limited, trading as Taylor & Francis Group.Taylor and Francis Ltd.2026Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/10679https://doi.org/10.1080/17568919.2026.27140281756-8919enFuture Medicinal Chemistryinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/10679