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

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Stefani HA, Gueogjan K, Manarin F, Farsky SH, Zukerman-Schpector J, Caracelli I, Pizano Rodrigues SR, Muscara MN, Teixeira SA, Santin JR, Machado ID, Bolonheis SM, Curi R, Vinolo MA

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

Eur J Med Chem. 2012 Dec;58:117-27. doi: 10.1016/j.ejmech.2012.10.010. Epub 2012 Oct 17.

PubMed ID
23123728 [ View in PubMed
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Abstract

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-alpha 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 pi...pi 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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(3S,5E)-3-propyl-3,4-dihydrothieno[2,3-f][1,4]oxazepin-5(2H)-imineNitric oxide synthase, endothelialIC 50 (nM)200N/AN/ADetails
ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATENitric oxide synthase, endothelialIC 50 (nM)58000N/AN/ADetails
ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATENitric oxide synthase, inducibleIC 50 (nM)350N/AN/ADetails