Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most
widely used therapeutics; they are competitive inhibitors of cyclooxygenase (COX), the enzyme
which mediates the conversion of arachidonic acid to inflammatory prostaglandins.
Objective: In this study, new benzodioxol derivatives with different core cycles and functional
groups (i.e., aryl acetate, aryl acetic acid and diazepine) were designed, synthesized, identified and
evaluated for their analgesic and anti-inflammatory activity, as a preliminary screening study to
identify the most potent and more selective groups.
Methods: The synthesized compounds were identified using FTIR, HRMS, 1H-NMR and 13C-NMR,
and evaluated for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase
(COX) inhibition assay kit.
Results and Discussion: Six compounds were synthesized as a preliminary screening study to identify
which was the most potent and more selective group towards COX-2 versus COX-1, compared
to ketoprofen as non-selective NSAIDs. The compounds have three different groups: aryl acetate,
aryl acetic acid and diazepine. The results showed that the most potent compound against the COX-
1 enzyme was 4b (which has diazepine and 2-chlorophenyl) with IC50 = 0.363 μM, and the selectivity
ratio of 4b was found to be better than ketoprofen. In contrast, compound 4a (which has diazepine
and 3-chlorophenyl) was the most selective with a COX-1/COX-2 ratio value of 0.85 in comparison
with a ketoprofen ratio value of 0.20.
Conclusion: In general, the synthesized library has moderate activity against both enzymes (i.e.,
COX-1 and COX-2). Moreover, all six compounds have better COX-2 inhibition selectivity compared
to the commercial drug ketoprofen.