Herein we present the design and the synthesis of novel substituted coumarin-benzimidazole/benzothiazole hybrids bearing a cyclic amidino group on the benzazole core as biologically active agents. All prepared compounds were evaluated for their in vitro antiviral and antioxidative activity as well as for their in vitro antiproliferative activity against a panel of several human cancer cell lines. Coumarin-benzimidazole hybrid 10 (EC50 9.0-43.8 μM) displayed the most promising broad spectrum antiviral activity, while two other coumarin-benzimidazole hybrids 13 and 14 showed the highest antioxidative capacity in the ABTS assay, superior to the reference standard BHT (IC50 0.17 and 0.11 mM, respectively). Computational analysis supported these results and demonstrated that these hybrids benefit from the high C-H hydrogen atom releasing tendency of the cationic amidine unit, and the pronounced ease with which they can liberate an electron, promoted by the electron-donating diethylamine group on the coumarin core. The coumarin ring substitution at position 7 with a N,N-diethylamino group also caused a significant enhancement of the antiproliferative activity, with the most active compounds being derivatives with a 2-imidazolinyl amidine group 13 (IC50 0.3-1.9 μM) and benzothiazole derivative with a hexacyclic amidine group 18 (IC50 1.3-2.0 μM).
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