The quest to find new antitumor compounds is an ongoing research endeavor in many laboratories around the world. The use of small-molecule angiogenesis inhibitors promises to be a potentially effective method for cancer treatment and possible prevention. Many antiangiogenic compounds are in various stages of laboratory evaluations and clinical trials. Curcumin is a natural product that has exhibited potent antiangiogenic properties. Based on a simple pharmacophore model, using standard drug design concepts, aromatic enone and aromatic dienone analogues of curcumin were prepared and/or obtained commercially. These compounds were screened for antiangiogenic properties via an in vitro SVR assay and were found to inhibit cell proliferation.