Oxazole and thiazole analogs of sulindac for cancer prevention.

Abstract

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.

• Authors: Bini Mathew, Judith V Hobrath, Michele C Connelly, R Kiplin Guy, Robert C Reynolds
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 10 Issue 7 Pg. 743-753 (04 01 2018) ISSN: 1756-8927 [Electronic] England
• PMID: 29671617 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

• Anti-Inflammatory Agents, Non-Steroidal (chemistry, therapeutic use)
• Antineoplastic Agents (chemistry, 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, chemistry, therapeutic use)
• Thiazoles (chemistry)