Cytotoxicity of salicylaldehyde benzoylhydrazone analogs and their transition metal complexes: quantitative structure-activity relationships

A series of salicylaldehyde benzoylhydrazone derivatives, their copper(II) complexes and a range of transition metal complexes of the unsubstituted li gand has been synthesized and evaluated for cytotoxicity against a human ad enocarcinoma cell line. A QSAR analysis revealed ligand cytotoxicity is str ongly correlated with electronic and transport factors and can be modeled b y treating each 'half' of the molecule as an isolated unit. Activity increa ses when substituents in the benzoyl ring were electron withdrawing whereas , for the salicylaldehyde ring, electron donation was required. The cytotox icity of the Cu(II) complexes was greater than, and paralleled the ligands. Activity for the transition metal complexes of the unsubstituted ligand mi rrored charge density on the metal. (C) 1999 Elsevier Science Inc. All righ ts reserved.