Synthesis and evaluation of dithiolethiones as novel cyclooxygenase inhibitors.

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Zanatta SD, Manallack DT, Jarrott B, Williams SJ

Synthesis and evaluation of dithiolethiones as novel cyclooxygenase inhibitors.

Bioorg Med Chem Lett. 2009 Jan 15;19(2):459-61. doi: 10.1016/j.bmcl.2008.11.045. Epub 2008 Nov 18.

PubMed ID

19056264 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rofecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	74.5	N/A	N/A	Details