Synthetic Chalcone Derivatives as Inhibitors of Cathepsins K and B, and Their Cytotoxic Evaluation

A series of chalcone derivatives, 1 – 15 , were prepared by ClaisenSchmidt condensation and evaluated for their cytotoxicities on tumor cell lines and also against proteolytic enzymes such as cathepsins B and K. Of the compounds synthesized, ( E )‐3‐(3,4‐dimethoxyphenyl)‐1‐phenylprop‐2‐en‐1‐one ( 12 ), ( E )‐3‐(4‐chlorophenyl)‐1‐phenylprop‐2‐en‐1‐one ( 13 ), ( E )‐3‐(4‐methoxyphenyl)‐1‐phenylprop‐2‐en‐1‐one ( 14 ), and ( E )‐3‐(4‐nitrophenyl)‐1‐phenylprop‐2‐en‐1‐one ( 15 ) showed significant cytotoxicities. The most effective compound was 15 , which showed high cytotoxic activity with an IC 50 value lower than 1 μg/ml, and no selectivity on the tumor cells evaluated. Substituents at C(4) of ring B were found to be essential for cytotoxicity. In addition, it was also demonstrated that some of these chalcones are moderate inhibitors of cathepsin K and have no activity against cathepsin B.