Title:Synthesis and Structure-activity Relationships of Chalcone Derivatives as Inhibitors of Ovarian Cancer Cell Growth
Volume: 14
Issue: 11
Author(s): Zachary D. Tucker, Francis J. Barrios and Amanda J. Krzysiak*
Affiliation:
- Department of Chemistry and Physics, Faculty of Chemistry, Bellarmine University, 2001 Newburg Rd., Louisville, KY,United States
Keywords:
Synthesis, chalcones, claisen-schmidt condensation, structure-activity, ovarian cancer, growth inhibition.
Abstract: Background: Ovarian cancer remains a disease with a poor five year survival rate. As
such, novel therapies are needed. Natural chalcones as well as their synthetic derivatives have
shown biological activity in a number of areas including the inhibition of cancer cell growth.
Objective: To synthesize a library of chalcone derivatives, including novel structures, and determiner
the inhibition of ovarian cancer cell growth and Structure-activity-relationships.
Methods: The Claisen-Schmidt condensation reaction between substituted acetophenones and aromatic
aldehydes was used to produce a series of novel chalcones in moderate to excellent yields and
good purity. Cellular proliferation of CA-OV3 cells was measured with a MTS assay.
Results: Out of the thirty-four synthesized compounds, eight are new derivatives. The synthesized
compounds were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation of these
β-phenylacrylophenone derivatives in CA-OV3 cells showed interesting antiproliferative activities
providing initial structure – activity information.
Conclusion: Fourteen of the thirty-four tested compounds showed significant activity, with several
showing near complete inhibition of growth at 100 µM. The structure-activity relationships suggest
that modification to the A ring is widely tolerated and that electron-donating modifications to the B
ring are beneficial to activity. Electron-withdrawing modifications to the B ring did not show inhibition
of cell growth.
