Benzazole Substituted Iminocoumarins as Potential Antioxidants with Antiproliferative Activity

(E-pub Ahead of Print)

Author(s): Nataša Perin, Maja Cindrić, Peter Vervaeke, Sandra Liekens, Tomislav Mašek, Kristina Starčević, Marijana Hranjec*

Journal Name: Medicinal Chemistry

Become EABM
Become Reviewer

Abstract:

Background: Benzazole and coumarine 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 offering thus 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.

Method: A series of coumarine derivatives containing a 2-benzazole motif was 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 beraing 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 displayed also selective activity toward CEM with submicromolar inhibitory concentration (0.059 µM; 0.17 ± 0.09, respectevly). 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 iminocoumarine 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, respectevly), which were chosen as lead compounds for further optimization and rational design to obtain ever more active and selective antiproliferative agents.

Keywords: Antioxidative Capacity, Antiproliferative Activity, Benzimidazoles, Benzotiazoles, Imidazo[4, 5-B]Pyridines, Iminocoumarins, Spectroscopy

Rights & PermissionsPrintExport Cite as

Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1573406416666191218101427
Price: $95

Article Metrics

PDF: 1