Cytotoxicity effects of transition-metal chelators of the 5-substituted 2-hydroxyacetophenones and their oximes

A series of 5-substituted 2-hydroxyacetophenones (A) and their oxime derivatives (B) were synthesized, and their cytotoxic activities towards MCF-7 breast cancer cells and B-16 melanoma cells were compared. The substitution on the benzylic position enabled variation of the lipophilic nature of the compound, while the chelating site remained free for metal binding. The results obtained indicate that the lipophilic properties of the compounds are favorable for cytotoxicity activity and that the oximes which are lipophilic enough (eg, B-4, B-5, B-9) are more potent than the corresponding ketones (A-4, A-5, A-9). All the potent oximes examined in this work showed strong cardiotoxicity.