Synthesis and Biological Evaluation of Benzodioxol Derivatives as Cyclooxygenase Inhibitors
Publication Type
Original research

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.

Letters in Drug Design & Discovery
Bentham Science Publishers B.V.
Publisher Country
United Arab Emirates
Thomson Reuters
Impact Factor
Publication Type
Both (Printed and Online)