Amine Containing Analogs of Sulindac for Cancer Prevention
Bini Mathew1, Judith V. Hobrath2, Michele C. Connelly3, R. Kiplin Guy4, Robert C. Reynolds5, *
Identifiers and Pagination:Year: 2018
First Page: 1
Last Page: 12
Publisher Id: TOMCJ-12-1
Article History:Received Date: 1/11/2017
Revision Received Date: 17/01/2018
Acceptance Date: 21/01/2018
Electronic publication date: 31/01/2018
Collection year: 2018
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4. 0 International Public License (CC-BY 4. 0), a copy of which is available at: https://creativecommons. org/licenses/by/4. 0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 activity in vitro and demonstrating in vivo xenograft activity.
Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.
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).
Several active compounds were identified viain vitro cancer cell line screening with the most potent compound (26) in the nanomolar range.
Compound 26 and analogs showing the most potent inhibitory activity may be considered for further design and optimization efforts as anticancer hit scaffolds.