Synthesis, evaluation and molecular docking studies for the anti-inflammatory activity of novel 8-substituted-7-benzoyloxy-4-methyl-6-nitrocoumarin derivatives
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abstract
Starting from the 8-acetyl-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoate I, 8-(3-arylacryloyl)-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoates (chalcones) II were synthesized and further used for the synthesis of two new series of 8-(2-imino/oxo/thioxo pyrimidin-4-yl)-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoates III-V and 8-(pyrazol-3-yl)-4-methyl-6-nitro-2-oxo-2H-chromen-7-yl benzoates VI and VII. All of the synthesized compounds were assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. The 8-acetyl coumarin I exhibited the most potent activity with 24.12% inhibition 2 h post carrageenan injection and 16.38% inhibition 3 h post carrageenan injection. In addition, an in silico comparative COX1 and COX2 docking study was performed in order to explain the possible interactions and the docking scores of all the compounds into the crystal structure of cyclooxygenases (Cox1 and Cox2) enzymes using Autodock 4.2 program. The results revealed more selective COX2 binding affinities of all the compounds over Cox1, whereas, only compound IVc exhibited non-selective COX1 and COX2 fitting.
