Arylation of 6-bromobenzo[b]thiophenes via Suzuki Miyaura cross-coupling: In silico insights into hemolytic, anti-biofilm, and anti-thrombolytic activities

In the current study, a series of 6-arylbenzo[b]thiophene derivatives (2a-2f) were prepared in good yields (76–91%) through Pd-catalyzed Suzuki cross-coupling, evaluated against hemolytic potential, biofilm inhibition, and antithrombotic activities. All compounds turned out to have significant biological activities. In particular, compound 2a revealed good hemolytic activity (28.8%) and compound 2b showed the highest antithrombolytic activity (54.17%). Compound 2c exhibited an excellent percentage inhibition value (86.23%). Moreover, absorption, distribution, metabolism, and excretion (ADME) predictions showed favorable pharmacokinetic profiles. All synthesized benzothiophenes were predicted to passively cross the blood-brain barrier and show exceptionally strong and consistent results for the entire series. Molecular docking analysis of benzothiophenes (2a-2f) exhibits strong binding affinities and close alignments of in-silico validation with hemolytic, biofilm, and thrombolytic target proteins, consistent with their experimental results. Furthermore, Network pharmacology was carried out to find out the multi-target mechanisms of the arylated 6-bromo-benzothiophenes (2a-2f). Gene Ontology enrichment analysis revealed that benzothiophene derivatives modulate coagulation, nitric oxide synthase activity, and immune signaling pathways, indicating strong cardioprotective, anti-inflammatory, and redox-regulatory potential. GRAPHICAL ABSTRACT