Amine Containing Analogs of Sulindac for Cancer Prevention

Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds (Lead / Corresponding author)

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Abstract

Background: Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activityin vitroand demonstratingin vivoxenograft activity.

Objective: Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method: A series of sulindac amine analogs were designed and synthesized and then further modified in a "libraries from libraries" approach to produce amide, sulfonamide and N,N-disubstituted sulindac amine sub-libraries. All analogs were screened against three cancer cell lines (prostate, colon and breast).

Results: Several active compounds were identifiedviain vitrocancer cell line screening with the most potent compound (26) in the nanomolar range.

Conclusion: Compound26and analogs showing the most potent inhibitory activity may be considered for further design and optimization efforts as anticancer hit scaffolds.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalOpen Medicinal Chemistry Journal
Volume12
Early online date31 Jan 2018
DOIs
Publication statusPublished - 31 Jan 2018

Keywords

  • Anticancer
  • Cancer
  • COX-independent
  • NSAIDs
  • Reverse amide
  • Sulfonamide
  • Sulindac

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  • Cite this

    Mathew, B., Hobrath, J. V., Connelly, M. C., Guy, R. K., & Reynolds, R. C. (2018). Amine Containing Analogs of Sulindac for Cancer Prevention. Open Medicinal Chemistry Journal, 12, 1-12. https://doi.org/10.2174/1874104501812010001