Angiogenesis is normally a highly regulated process that occurs during development, reproduction, and wound repair. However, angiogenesis can also become a fundamental pathogenic process in cancer and several other diseases. To date, the synthesis of angiogenesis inhibitors has been researched in several ways also starting from bioactive plant compounds. In the present study, we tested both in an angiogenesis bioassay and in ovarian cell culture, the potential antiangiogenic effect of a natural-derived benzo[k,l]xanthene lignan (5). This unusual compound was synthesized through the biomimetic dimerization of CAPE (caffeic acid phenethyl ester), a bioactive component of honeybee propolis. The lignan showed a significant, dose-related inhibitory effect on new vessel growth in the angiogenesis bioassay and it inhibited Vascular Endothelial Growth Factor secretion in ovarian cell culture. Therefore, we indicate the natural-derived benzo[k,l]xanthene lignan 5 as a potential new angiogenesis inhibitor.