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

Bini Mathew; Timothy S. Snowden; Michele C. Connelly; R. Kiplin Guy; Robert C. Reynolds

doi:10.1016/j.bmcl.2018.05.023

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

Bini Mathew, Timothy S. Snowden, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English
Pages (from-to)	2136-2142
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	28
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2018.05.023
State	Published - Jul 1 2018

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health NCI 1R01CA131378 (RCR PI) and DOD Era of Hope award W81XWH-07-1-0463 (RCR PI). We thank Lucile White, Lynn Rasmussen and Melinda Ingram of Southern Research for HTS support services. Additionally, Judith V. Hobrath of the Drug Discovery Unit in the College of Life Sciences at the University of Dundee gave critical input into manuscript preparation and provided information relative to metabolism of the sulindac analogs presented in this work. We would also like to acknowledge contributions by the High Throughput Biology Center in the Department of Chemical Biology and Therapeutics at St. Jude Children’s Research Hospital in Memphis, TN for BJ cell line data and additional anticancer cell line screens. The work at St. Jude was supported by American Lebanese Syrian Associated Charities (ALSAC).

Publisher Copyright:
© 2018 The Authors

Keywords

Anticancer
Chemical biology
Chemoprevention
Profens
Sulindac

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2018.05.023

Cite this

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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.",

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note = "Funding Information: This work was supported by grants from the National Institutes of Health NCI 1R01CA131378 (RCR PI) and DOD Era of Hope award W81XWH-07-1-0463 (RCR PI). We thank Lucile White, Lynn Rasmussen and Melinda Ingram of Southern Research for HTS support services. Additionally, Judith V. Hobrath of the Drug Discovery Unit in the College of Life Sciences at the University of Dundee gave critical input into manuscript preparation and provided information relative to metabolism of the sulindac analogs presented in this work. We would also like to acknowledge contributions by the High Throughput Biology Center in the Department of Chemical Biology and Therapeutics at St. Jude Children{\textquoteright}s Research Hospital in Memphis, TN for BJ cell line data and additional anticancer cell line screens. The work at St. Jude was supported by American Lebanese Syrian Associated Charities (ALSAC). Publisher Copyright: {\textcopyright} 2018 The Authors",

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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