1. 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.
- Author
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Zhang, Xiaojie, Wang, Rubing, Perez, German Ruiz, Chen, Guanglin, Zhang, Qiang, Zheng, Shilong, Wang, Guangdi, and Chen, Qiao-Hong
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DRUG design , *DRUG synthesis , *TETRAENES , *CANCER chemotherapy , *PROSTATE cancer treatment , *DRUG efficacy - 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]
- Published
- 2016
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