Design, synthesis, antitrypanosomal activity, DNA/RNA binding and in vitro ADME profiling of novel imidazoline-substituted 2-arylbenzimidazoles

摘要: Abstract Novel imidazoline benzimidazole derivatives containing diversely substituted phenoxy moieties were synthesized with the aim of evaluating their antitrypanosomal activity, DNA/RNA binding affinity and in vitro ADME properties. The presence diethylaminoethyl subunit in 18a–18c led to enhanced potency, particularly for 18a 18c, which contain unsubstituted methoxy-substituted moieties. They found be > 2-fold more potent against African trypanosomes than nifurtimox. Fluorescence CD spectroscopy, thermal denaturation assays computational analysis indicated a preference toward AT-rich DNA minor groove mode. Replacement amidine group less basic ionisable nitrogen-containing failed improve membrane permeability investigated compounds. Due structural diversification, compounds displayed range physico-chemical features resulting variable properties, leaving space further optimization biological profiles.