Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity |
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| Authors: | Liridona Useini Marija Mojić Dr. Markus Laube Dr. Peter Lönnecke Dr. Sanja Mijatović Dr. Danijela Maksimović-Ivanić Prof. Dr. Jens Pietzsch Prof. Dr. Dr. h.c. mult. Evamarie Hey-Hawkins |
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| Affiliation: | 1. Faculty of Chemistry and Mineralogy, Institute of Inorganic Chemistry, Leipzig University, 04103 Leipzig, Germany;2. Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia;3. Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany |
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| 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. |
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| Keywords: | Carborane cancer COX inhibitors drug design fenoprofen |
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