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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
- 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 (1E,3E,6E,8E)-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 G0/G1 phase.
- Subjects :
- 0301 basic medicine
Male
Curcumin
Clinical Biochemistry
Pharmaceutical Science
Antineoplastic Agents
Apoptosis
Biochemistry
Article
03 medical and health sciences
chemistry.chemical_compound
Prostate cancer
0302 clinical medicine
Cell Line, Tumor
Drug Discovery
medicine
Potency
Humans
Molecular Biology
Cell Proliferation
Cell growth
Organic Chemistry
Cell Cycle
Prostate
Cancer
Prostatic Neoplasms
Cell cycle
medicine.disease
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Drug Design
Wittig reaction
Cancer research
Molecular Medicine
Drug Screening Assays, Antitumor
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....4b8a3d0c307a80ecfc9620dff6b2b9e7