Carboranyl analogues of mefenamic acid and their biological evaluation

Mefenamic acid represents a widely used nonsteroidal anti-inflammatory drug (NSAID) to treat pain of postoperative sur-gery and heavy menstrual bleeding. Like other NSAIDs, mefenamic acid inhibits the synthesis of prostaglandins by non-selectively blocking cyclooxygenase (COX) isoforms COX-1 and COX-2. For improved selectivity of the drug and thereby reduced related side effects, the carborane analogues of mefenamic acid were evaluated. The ortho-, meta- and para-carborane derivatives were synthesized in three steps: halogenation of the respective cluster, followed by a Pd-catalyzed B–N coupling and hydrolysis of the nitrile derivatives under acidic conditions. COX inhibitory activity and cytotoxicity for different cancer cell lines revealed that the carborane analogues have stronger anti-tumor potential compared to their parent organic compound.