A Structure‐Activity Relationship Study of Amino Acid Derivatives of Pterostilbene Analogues Toward Human Breast Cancer

Abstract Pterostilbene is the dimethylated analogue of Resveratrol, a compound with well‐known biological activities, such as antioxidant, chemopreventive, anti‐diabetic, anti‐obesity, and cardioprotective. Despite many studies on the general effect of such polyphenolic molecules and their derivatives, a deep comprehension of their action and systematic structure‐activity relationship studies are still rare. Herein, three different analogues of functionalizable Pterostilbene were efficiently synthesized and derivatized with a selected library of antioxidant amino acids, allowing for a highly diversified exploration of the chemical space. The library was analyzed towards cancer cells. Collectively, our data demonstrated the enhanced anti‐proliferative activity of Tryptophan‐conjugated compounds. In breast cancer cells, the treatment with Tryptophan‐conjugated analogues induced the activation of cellular stress pathways, including autophagy signaling.