title: Synthesis and evaluation of carbaborane derivatives of indomethacin as cyclooxygenase inhibitors.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological activities by inhibiting cyclooxygenase (COX)-1 and COX-2. Previous studies have shown that esters and amides of non-selective inhibitors such as indomethacin are selective against COX-2, which is the therapeutically relevant isoform. Structure-activity analysis indicates that substituted phenyl rings are tolerated as ester components. In the present study, the introduction of inorganic ortho- and meta-carbaborane moieties was explored with the aim to create COX-2 inhibitors and more importantly to investigate the validity of using these boron clusters as drug entities. Interestingly, only the ortho-carbaborane ester was active whereas the meta isomer was not. A similar lack of inhibitory potency was observed when an adamantyl substituent or alkylene spacers at the carbaborane were introduced in the ester functionality.
authors.affiliation: Institut für Anorganische Chemie der Universität Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scholz
authors.forename: Anna L
authors.initials: AL
authors.lastname: Blobaum
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.forename: Evamarie
authors.initials: E
authors.lastname: Hey-Hawkins
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000031:analogs & derivatives*; D008958:Models, Molecular
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin