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

摘要: In search of more effective chemotherapeutics for the treatment 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 Horner-Wadsworth-Emmons reaction. Twenty-three them are new compounds. The WST-1 cell proliferation assay was employed to assess their anti-proliferative effects toward both androgen-sensitive androgen-insensitive human lines. Eighteen out twenty-five compounds possess significantly improved potency as compared with curcumin. optimal compound, 78, is 14- 23-fold potent than in inhibiting proliferation. It can be concluded from our data that 1,9-diarylnona-1,3,6,8-tetraen-5-one serve a potential scaffold development anti-prostate agents pyridine-4-yls quinolin-4-yl act enhanced this scaffold. Two most compounds, 68 75, effectively suppress PC-3 activating apoptosis arresting cycle G0/G1 phase.