73242-06-5Relevant academic research and scientific papers
Synthesis, anti-inflammatory activity, and in vitro antitumor effect of a novel class of cyclooxygenase inhibitors: 4-(Aryloyl)phenyl methyl sulfones
Harrak, Youssef,Casula, Giovanni,Basset, Joan,Rosell, Glòria,Plescia, Salvatore,Raffa, Demetrio,Cusimano, Maria Grazia,Pouplana, Ramon,Pujol, Maria Dolors
supporting information; experimental part, p. 6560 - 6571 (2010/11/04)
Following our previous research on anti-inflammatory drugs (NSAIDs), we report on the design and synthesis of 4-(aryloyl)phenyl methyl sulfones. These substances were characterized for their capacity to inhibit cyclooxygenase (COX-1 and COX-2) isoenzymes. Molecular modeling studies showed that the methylsulfone group of these compounds was inserted deep in the pocket of the human COX-2 binding site, in an orientation that precludes hydrogen bonding with Arg120, Ser353, and Tyr355 through their oxygen atoms. The N-arylindole 33 was the most potent inhibitor of COX-2 and also the most selective (COX-1/COX-2 IC50 ratio was 262). The indole derivative 33 was further tested in vivo for its anti-inflammatory activity in rats. This compound showed greater inhibitory activity than ibuprofen. Other compounds (20, 26, 9, and 30) showed strong activity against carrageenan-induced inflammation. The latter compounds showed a weak capacity to inhibit the proliferation of human cell lines K562, NCI-H460, and HT-29 in vitro.
