Oxazole and thiazole analogs of sulindac for cancer prevention

Aim: Experimental and epidemiological studies and clinical trials suggest that nonsteroidalanti-inflammatory drugs possess antitumor potential. Sulindac, a widely used nonsteroidalanti-inflammatory drug, can prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindacsulfide amide(SSA) is an amide-linked sulindacsulfide analog that showed in vivo antitumor activity in a human colon tumor xenograft model. Results/methodology: A new analog series with heterocyclic rings such as oxazoleor thiazoleat the C-2 position of sulindacwas prepared and screened against prostate, colon and breast cancer cell lines to probe the effect of these novel substitutions on the activity of sulindacanalogs. Conclusion: In general, replacement of the amidefunction of SSA analogs had a negative impact on the cell lines tested. A small number of hits incorporating rigid oxazoleor thiazolegroups in the sulindacscaffold in place of the amidelinkage show co...