Synthesis and evaluation of dithiolethiones as novel cyclooxygenase inhibitors

Shannon D Zanatta, David Thomas Manallack, Bevyn Jarrott, Spencer J Williams

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)


3H-1,2-Dithiole-3-thiones substituted with a 3,5-di-tert-butyl-4-hydroxyphenyl (DTBHP) or a 3,5-di-tert-butyl-4-methoxyphenyl group at the C5 position were prepared and their ability to inhibit the cyclooxygenase isoenzymes, COX-1 and COX-2 was evaluated. Both compounds were potent inhibitors of COX-2 (relative to rofecoxib), and while the phenol was a weak inhibitor of COX-1, the methyl ether gave no measurable inhibition. Docking studies of the two compounds into the COX-1 and -2 active sites showed that the methyl ether could only fit in the COX-2 active site whereas the phenol could be docked into both COX-1 and -2. This study reports a new mode for inhibitor binding to COX-1 and -2 and a novel structural scaffold for the development of COX-2 selective inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)459 - 461
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Issue number2
Publication statusPublished - 2009

Cite this