Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation

Mefenamic acid represents
a widely used nonsteroidal anti-inflammatory
drug (NSAID) to treat the pain of postoperative surgery and heavy
menstrual bleeding. Like other NSAIDs, mefenamic acid inhibits the
synthesis of prostaglandins by nonselectively blocking cyclooxygenase
(COX) isoforms COX-1 and COX-2. For the improved selectivity of the
drug and, therefore, 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. The COX inhibitory activity
and cytotoxicity for different cancer cell lines revealed that the
carborane analogues have stronger antitumor potential compared to
their parent organic compound.