A series of chalcone derivatives, 1-15, were prepared by Claisen-Schmidt 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 IC50 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.

Synthetic Chalcone Derivatives as Inhibitors of Cathepsins K and B, and Their Cytotoxic Evaluation. -A number of known chalcone derivatives bearing different aromatic substituents is synthesized and tested for their biological activity. The highest cytotoxic activity is observed for (IIIa). -(RAMALHO, S. D.; BERNADES, A.; DEMETRIUS, G.; NODA-PEREZ*, C.; VIEIRA, P. C.; DOS SANTOS, C. Y.; DA SILVA, J. A.; DE MORAES, M. O.; MOUSINHO, K. C.; Chem. Biodiversity 10 (2013) 11, 1999-2006, http://dx.