Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity

Abstract Fenoprofen is a widely used nonsteroidal anti‐inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX‐1 the “house‐keeping” enzyme and COX‐2 the induced isoform from pathological stimuli. Unselective inhibition of both COX isoforms results in many side effects, but off‐target effects have also been reported. The steric modifications of the drugs could afford the desired COX‐2 selectivity. Furthermore, NSAIDs have shown promising cytotoxic properties. The structural modification of fenoprofen using bulky dicarba‐ closo ‐dodecaborane(12) (carborane) clusters and the biological evaluation of the carborane analogues for COX inhibition and antitumor potential showed that the carborane analogues exhibit stronger antitumor potential compared to their respective aryl‐based compounds.