Background: Benzazole and coumarin derivatives are one of the most privileged heterocyclic
substructures in the medicinal chemistry with well-known biological features, which include
a wide range of versatile biological activities as well as excellent spectroscopic characteristics
thus offering their potential application in many research fields.
Objective: The prepared iminocoumarins were synthesized to evaluate their antioxidative potential
by using ABTS and FRAP assays and in vitro antiproliferative activity.
Methods: A series of coumarin derivatives containing a 2-benzazole motif were synthesized and
evaluated for their antioxidative capacity and antiproliferative activity. Their molecular structure
incorporates a push-pull functionality: an electron donor donating group at the 7-position with an
electron-withdrawing group, such as benzimidazole, benzothiazole and imidazopyridine fragment
at the 3-position.
Results: The iminocoumarins bearing different substituents on 7-position were evaluated for their
antiproliferative activity on tree cancer cells with only 4 compounds showing the antiproliferative
activity. The most active derivative was N,N-diethylamino substituted benzimidazole derivative 4d
and imidazo[4,5-b]pyridine analogue 6b, both also displayed selective activity toward CEM with
submicromolar inhibitory concentration (0.059 μM; 0.17 ± 0.09, respectively). The inhibitory effect
of 4d and 6b derivatives on the cell-cycle progression of HeLa cells was studied. A flow cytometric
analysis of the HeLa cells indicated an appreciable cell-cycle arrest in a dose-dependent
manner. Antioxidant properties were studied by ABTS and FRAP assays and obtained results revealed
that the most promising antioxidant has proven to be compound 3b while other compounds,
in general, showed moderate to very low antioxidative capacity in both assays.
Conclusion: Unsubstituted benzimidazole derivatives bearing hydroxyl group on iminocoumarin
nuclei exhibited the most prominent antioxidant potential in ABTS assay (3b; 40.5 ± 0.01). The
most significant and selective antiproliferative activity was displayed by compounds 4d and 6b
(0.059 μM; 0.17 ± 0.09, respectively), which were chosen as lead compounds for further optimization
and rational design to obtain more active and selective antiproliferative agents.