Oxazole and thiazole analogs of sulindac for cancer prevention

Future Med Chem. 2018 Apr 1;10(7):743-753. doi: 10.4155/fmc-2017-0182. Epub 2018 Apr 19.


Aim: Experimental and epidemiological studies and clinical trials suggest that nonsteroidal anti-inflammatory drugs possess antitumor potential. Sulindac, a widely used nonsteroidal anti-inflammatory drug, can prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA) is an amide-linked sulindac sulfide 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 oxazole or thiazole at the C-2 position of sulindac was prepared and screened against prostate, colon and breast cancer cell lines to probe the effect of these novel substitutions on the activity of sulindac analogs.

Conclusion: In general, replacement of the amide function of SSA analogs had a negative impact on the cell lines tested. A small number of hits incorporating rigid oxazole or thiazole groups in the sulindac scaffold in place of the amide linkage show comparable activity to our lead agent SSA.

Keywords: NSAIDs; cancer; heterocycles; oxazole; sulindac; thiazole.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Female
  • Heterografts
  • Humans
  • Male
  • Neoplasms / prevention & control*
  • Oxazoles / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Spectrometry, Mass, Electrospray Ionization
  • Sulindac / analogs & derivatives*
  • Sulindac / chemistry
  • Sulindac / therapeutic use*
  • Thiazoles / chemistry*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Oxazoles
  • Thiazoles
  • sulindac sulfide amide
  • Sulindac