Oxazole and thiazole analogs of sulindac for cancer prevention.
| Autor: | Mathew B; Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA., Hobrath JV; Drug Discovery Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK., Connelly MC; Department of Chemical Biology & Therapeutics, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mailstop 1000, Memphis, TN 38105-3678 USA., Guy RK; The University of Kentucky College of Pharmacy, 214H BioPharm Complex, Lexington, KY 40536-0596, USA., Reynolds RC; Division of Hematology & Oncology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Future medicinal chemistry [Future Med Chem] 2018 Apr 01; Vol. 10 (7), pp. 743-753. Date of Electronic Publication: 2018 Apr 19. |
| DOI: | 10.4155/fmc-2017-0182 |
| Abstrakt: | Aim: Experimental and epidemiological studies and clinical trials suggest that nonsteroidal anti-inflammatory drugs possess antitumor potential. Sulindac, a widely used nonsteroidal anti-inflammatory drug, can prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA) is an amide-linked sulindac sulfide analog that showed in vivo antitumor activity in a human colon tumor xenograft model. Results/methodology: A new analog series with heterocyclic rings such as oxazole or thiazole at the C-2 position of sulindac was prepared and screened against prostate, colon and breast cancer cell lines to probe the effect of these novel substitutions on the activity of sulindac analogs. Conclusion: In general, replacement of the amide function of SSA analogs had a negative impact on the cell lines tested. A small number of hits incorporating rigid oxazole or thiazole groups in the sulindac scaffold in place of the amide linkage show comparable activity to our lead agent SSA. |
| Databáze: | MEDLINE |
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