Synthesis and Structure-activity Relationships of Chalcone Derivatives as Inhibitors of Ovarian Cancer Cell Growth

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. Keywords: Synthesis, chalcones, claisen-schmidt condensation, structure-activity, ovarian cancer, growth inhibition.