Synthesis, biological evaluation and molecular docking studies of 3-(triazolyl)-coumarin derivatives: Effect on inducible nitric oxide synthase

A series of 3-(triazolyl)-coumarins were synthesized and tested as anti-inflammatory agents. It was possible to infer that these compounds do not alter the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways involved in the TNF-α secretion and COX-2 activity were not affected. Nevertheless, the compounds inhibited iNOS-derived NO production, without affecting the eNOS activity. The outcome of the docking studies showed that π⋯π interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Moreover, the efficacy of this compound was visualized by the reduced number of neutrophils in the LPS-inflamed subcutaneous tissue. Together, biological and docking data show that triazolyl-substituted coumarins, that can act on iNOS, are a good scaffold to be explored.

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► New 3-(triazolyl) substituted coumarins were synthesized.
► The phenyl substituted compound presented a higher inhibitory action on iNOS.
► Molecular docking studies were carried out in the crystal structures of eNOS and iNOS.
► 3c is a very promising compound as results suggest that it is a selective agent for iNOS.