Synthesis and biological evaluation of novel synthetic chalcone derivatives as anti-tumor agents targeting Cat L and Cat K.

A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and 143B cell lines in vitro. SAR analysis showed that compounds bearing a benzenesulfonamide group had greater potency than those bearing a benzamide group. It was also shown that compounds with a mono-methyl or mono-halogen group at the 3-position on the terminal phenyl ring were more effective than those with trifluoromethyl or methoxy groups. Compound 8e exhibited the most potent anti-tumor activities against HCT116, MCF7 and 143B cell lines, with IC50 values of 0.597, 0.886 and 0.791µM, respectively. Molecular docking studies and enzymatic assays demonstrated that the anti-tumor activity of compound 8e might be regulated by Cat L and Cat K.