Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation

  • ACS Omega. 2022 Jun 29;7(28):24282-24291. doi: 10.1021/acsomega.2c01523.
Liridona Useini  1 ,  Marija Mojić  2 ,  Markus Laube  3 ,  Peter Lönnecke  1 ,  Jonas Dahme  4 ,  Menyhárt B Sárosi  4 ,  Sanja Mijatović  2 ,  Danijela Maksimović-Ivanić  2 ,  Jens Pietzsch  3  5 ,  Evamarie Hey-Hawkins  1
Affiliations
  • 1. Faculty of Chemistry and Mineralogy, Institute of Inorganic Chemistry, Leipzig University, Johannisallee 29, 04103 Leipzig, Germany.
  • 2. Department of Immunology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Bul. Despota Stefana 142, 11060 Belgrade, Serbia.
  • 3. Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Bautzner Landstrasse 400, 01328 Dresden, Germany.
  • 4. Wilhelm-Ostwald-Institute for Physical and Theoretical Chemistry, Leipzig University, Linnéstraße 2, 04103 Leipzig, Germany.
  • 5. Faculty of Chemistry and Food Chemistry, School of Science, Technical University Dresden, 01069 Dresden, Germany.
PMID: 35874202 DOI: 10.1021/acsomega.2c01523
Abstract

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.

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