Diverse amide analogs of sulindac for cancer treatment and prevention

Bini Mathew; Judith V. Hobrath; Michele C. Connelly; R. Kiplin Guy; Robert C. Reynolds

doi:10.1016/j.bmcl.2017.09.022

Diverse amide analogs of sulindac for cancer treatment and prevention

Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

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

22 Scopus citations

Abstract

Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivo antitumor activity that was comparable to sulindac in a human colon tumor xenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good activity relative to the parent (1), including five analogs that also possess nanomolar inhibitory potencies against acute lymphoblastic leukemia cells. Several new analogs identified may serve as anticancer lead candidates for further development.

Original language	English
Pages (from-to)	4614-4621
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	27
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2017.09.022
State	Published - 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s)

Funding

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 for HTS support services. 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).

Funders	Funder number
DOD Era of Hope	W81XWH-07-1-0463
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R01CA131378
American Lebanese Syrian Associated Charities

Keywords

Amides
Cancer
NSAIDs
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)

Access to Document

10.1016/j.bmcl.2017.09.022

Cite this

@article{33a787b0e54747f59ab4841027c5a234,

title = "Diverse amide analogs of sulindac for cancer treatment and prevention",

abstract = "Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivo antitumor activity that was comparable to sulindac in a human colon tumor xenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good activity relative to the parent (1), including five analogs that also possess nanomolar inhibitory potencies against acute lymphoblastic leukemia cells. Several new analogs identified may serve as anticancer lead candidates for further development.",

keywords = "Amides, Cancer, NSAIDs, Sulindac",

author = "Bini Mathew and Hobrath, \{Judith V.\} and Connelly, \{Michele C.\} and \{Kiplin Guy\}, R. and Reynolds, \{Robert C.\}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s)",

year = "2017",

doi = "10.1016/j.bmcl.2017.09.022",

language = "English",

volume = "27",

pages = "4614--4621",

number = "20",

}

TY - JOUR

T1 - Diverse amide analogs of sulindac for cancer treatment and prevention

AU - Mathew, Bini

AU - Hobrath, Judith V.

AU - Connelly, Michele C.

AU - Kiplin Guy, R.

AU - Reynolds, Robert C.

PY - 2017

Y1 - 2017

N2 - Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivo antitumor activity that was comparable to sulindac in a human colon tumor xenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good activity relative to the parent (1), including five analogs that also possess nanomolar inhibitory potencies against acute lymphoblastic leukemia cells. Several new analogs identified may serve as anticancer lead candidates for further development.

AB - Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivo antitumor activity that was comparable to sulindac in a human colon tumor xenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good activity relative to the parent (1), including five analogs that also possess nanomolar inhibitory potencies against acute lymphoblastic leukemia cells. Several new analogs identified may serve as anticancer lead candidates for further development.

KW - Amides

KW - Cancer

KW - NSAIDs

KW - Sulindac

UR - http://www.scopus.com/inward/record.url?scp=85029523205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029523205&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2017.09.022

DO - 10.1016/j.bmcl.2017.09.022

M3 - Article

C2 - 28935266

AN - SCOPUS:85029523205

SN - 0960-894X

VL - 27

SP - 4614

EP - 4621

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 20

ER -

Diverse amide analogs of sulindac for cancer treatment and prevention

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this