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Design, synthesis, and biological evaluation of 1,9-diheteroarylnona-1,3,6,8-tetraen-5-ones as a new class of anti-prostate cancer agents.
- Source :
-
Bioorganic & Medicinal Chemistry . Oct2016, Vol. 24 Issue 19, p4692-4700. 9p. - Publication Year :
- 2016
-
Abstract
- In search of more effective chemotherapeutics for the treatment of castration-resistant prostate cancer and inspired by curcumin analogues, twenty five (1 E ,3 E ,6 E ,8 E )-1,9-diarylnona-1,3,6,8-tetraen-5-ones bearing two identical terminal heteroaromatic rings have been successfully synthesized through Wittig reaction followed by Horner–Wadsworth–Emmons reaction. Twenty-three of them are new compounds. The WST-1 cell proliferation assay was employed to assess their anti-proliferative effects toward both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Eighteen out of twenty-five synthesized compounds possess significantly improved potency as compared with curcumin. The optimal compound, 78 , is 14- to 23-fold more potent than curcumin in inhibiting prostate cancer cell proliferation. It can be concluded from our data that 1,9-diarylnona-1,3,6,8-tetraen-5-one can serve as a new potential scaffold for the development of anti-prostate cancer agents and that pyridine-4-yls and quinolin-4-yl act as optimal heteroaromatic rings for the enhanced potency of this scaffold. Two of the most potent compounds, 68 and 75 , effectively suppress PC-3 cell proliferation by activating cell apoptosis and by arresting cell cycle in the G 0 /G 1 phase. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 24
- Issue :
- 19
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 117895276
- Full Text :
- https://doi.org/10.1016/j.bmc.2016.08.006