Dual Relaxant Effect of Coumarin-3-carboxamides Through the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and Ca2+ Channels Blockade.

Abstract

We aimed to determine the relaxant pathway of seventeen synthetic compounds derived from coumarin-3-carboxamide. An isolated rat aorta assay was used. To determine the vasorelaxant mode of action, receptor blockers and specific enzyme inhibitors involved in endothelial and smooth muscle signaling pathways were used. The compounds 2, 4, and 5 showed higher activity than the other compounds. N-nitro-L-arginine methyl ester (10 µM) and methylene blue (10 µM) significantly inhibited the relaxant effect of the compounds 2, 4, and 5 (p ≤ 0.05), but not tetraethylammonium (5 mM), indomethacin (10 µM), or atropine (1 µM). The compounds 2, 4, and 5 abated the contraction induced by CaCl₂. The compounds 2, 4, and 5 exert a relaxing effect through the nitric oxide/cyclic guanosine monophosphate pathway activation and by blocking Ca²⁺ channels of the cell membrane. These findings propose coumarin-3-carboxamides as new drug entities with the potential to develop non-clinical and clinical.