LAUSR

A new class of pyrazino[1,2‐a]benzimidazole derivatives possessing the SO2Me pharmacophore at the para position of the C‐3 phenyl ring was designed, synthesized, and tested for their cyclooxygenase‐2 (COX‐2) inhibitory, anti‐cancer and anti‐platelet aggregation activities. In vitro COX‐1/COX‐2 inhibition studies showed that 2‐(4‐methylphenyl)‐1‐methylene‐3‐(4‐(methylsulfonyl)phenyl)‐1,2‐dihydropyrazino‐[1,2‐a]benzimidazole (5g) was the most potent COX‐2 inhibitor (IC50 = 0.08 μM) and 2‐(3,4,5‐trimethoxyphenyl)‐1‐methylene‐3‐(4‐(methylsulfonyl)phenyl)‐1,2‐dihydropyrazino‐[1,2‐a]benzimidazole (5m) had the highest selectivity index (SI > 909). Cytotoxicity of the synthesized compounds was also determined against the MCF‐7 cell line. Most compounds were cytotoxic against MCF‐7 cells and our results showed that compound 5m exhibited the highest anti‐proliferative activity compared to the reference compound, cisplatin. Our data also indicated that compound 5k was the most potent platelet aggregation inhibitor according to aggregometry test results.