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 ligand has been synthesized and evaluated for cytotoxicity against a human adenocarcinoma cell line. A QSAR analysis revealed ligand cytotoxicity is strongly correlated with electronic and transport factors and can be modeled by treating each 'half' of the molecule as an isolated unit. Activity increases when substituents in the benzoyl ring were electron withdrawing whereas, for the salicylaldehyde ring, electron donation was required. The cytotoxicity of the Cu(II) complexes was greater than, and paralleled the ligands. Activity for the transition metal complexes of the unsubstituted ligand mirrored charge density on the metal.
Ainscough
E W
EW
Department of Chemistry, Massey University, Palmerston North, New Zealand.
Brodie
A M
AM
Denny
W A
WA
Finlay
G J
GJ
Gothe
S A
SA
Ranford
J D
JD
D001547:Benzaldehydes / Q000737:chemistry*; D003300:Copper; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D013329:Structure-Activity Relationship
D001547:Benzaldehydes; D006835:Hydrazones; D008024:Ligands; C073458:salicylaldehyde benzoyl hydrazone; D003300:Copper