A small diversity library of α-methyl amide analogs of sulindac for probing anticancer structure-activity relationships

  • Bioorg Med Chem Lett. 2018 Jul 1;28(12):2136-2142. doi: 10.1016/j.bmcl.2018.05.023.
Bini Mathew  1 ,  Timothy S Snowden  2 ,  Michele C Connelly  3 ,  R Kiplin Guy  4 ,  Robert C Reynolds  5
Affiliations
  • 1. Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA.
  • 2. Department of Chemistry and Biochemistry, The University of Alabama, 250 Hackberry Lane, Tuscaloosa, AL 35487, USA.
  • 3. Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mailstop 1000, Memphis, TN 38105-3678, USA.
  • 4. The University of Kentucky College of Pharmacy, 214H BioPharm Complex, Lexington, KY 40536-0596, USA.
  • 5. Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: [email protected].
PMID: 29776741 DOI: 10.1016/j.bmcl.2018.05.023
Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) have a variety of potential indications that include management of pain and inflammation as well as chemoprevention and/or treatment of Cancer. Furthermore, a specific form of ibuprofen, dexibuprofen or the S-(+) form, shows interesting neurological activities and has been proposed for the treatment of Alzheimer's disease. In a continuation of our work probing the Anticancer activity of small sulindac libraries, we have prepared and screened a small diversity library of α-methyl substituted sulindac amides in the profen class. Several compounds of this series displayed promising activity compared with a lead sulindac analog.

Keywords
Anticancer; Chemical biology; Chemoprevention; Profens; Sulindac.