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

[Display omitted] •Anticancer activities of 60 new α-Me analogs of sulindac sulfide amide are reported.•Several compounds (6–29 and 60) show comparable inhibition of prostate, colon, breast cancer.•Addition of an α-methyl group to the lead scaffold does not dramatically alter activity.•Several analo...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2018-07, Vol.28 (12), p.2136-2142
Main Authors: Mathew, Bini, Snowden, Timothy S., Connelly, Michele C., Guy, R. Kiplin, Reynolds, Robert C.
Format: Article
Language:English
Subjects:
Amides - chemical synthesis
Amides - chemistry
Amides - pharmacology
Animals
Anticancer
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line
Cell Proliferation - drug effects
Chemical biology
Chemoprevention
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Mice
Molecular Structure
Neoplasms, Experimental - drug therapy
Neoplasms, Experimental - pathology
Profens
Small Molecule Libraries - chemical synthesis
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Structure-Activity Relationship
Sulindac
Sulindac - chemical synthesis
Sulindac - chemistry
Sulindac - pharmacology
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Summary:[Display omitted] •Anticancer activities of 60 new α-Me analogs of sulindac sulfide amide are reported.•Several compounds (6–29 and 60) show comparable inhibition of prostate, colon, breast cancer.•Addition of an α-methyl group to the lead scaffold does not dramatically alter activity.•Several analogs (6, 8, 11, 14, 20, 21, 24, 29, 57) show activity against several other cell lines.•Separated isomers, 5 and epi-5, show similar activities. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2018.05.023