A set of 1,2,4-triazine derivatives were designed as cyclooxygenase-2 (COX-2) inhibitors. These compounds were synthesized and screened for inhibition of cyclooxygenases (COX-1 and COX-2) based on a cellular assay using human whole blood (HWB) and lipoxygenase (LOX-15) that are key enzymes in inFammation. The results showed that 3-(2-(benzo-bis(4-methoxyphenyl)-1,2,4-triazine (G11) was identified as the most potent COX-2 inhibitor (78%) relative to COX-1 (50%). Ferric reducing anti-oxidant power (FRAP) assay revealed that compound G10 possesses the highest anti-oxidant activity. The compound G3 with IC 50 value of 124 mM was the most potent compound in LOX inhibitory assay. Molecular docking was performed and a good agreement was observed between computational and experimental results.