Highly cytotoxic DNA-interacting copper(ii) coordination compounds

Abstract

Four new Schiff-base ligands have been designed and prepared by condensation reaction between hydrazine derivatives (i.e. 2-hydrazinopyridine or 2-hydrazinoquinoline) and mono- or dialdehyde (3-tert-butyl-2-hydroxybenzaldehyde and 5-tert-butyl-2-hydroxyisophthalaldehyde, respectively). Six copper(II) coordination compounds of various nuclearities have been obtained from these ligands, which are formulated as [Cu(L1)Cl](CH₃OH) (1), [Cu(L2)NO₃] (2), [Cu₂(L3)(ClO₄)₂(CH₃O)(CH₃OH)](CH₃OH) (3), [Cu₂(L4)(ClO₄)(OH)(CH₃OH)](ClO₄) (4), [Cu₈(L3)₄(NO₃)₄(OH)₅](NO₃)₃(CH₃OH)₅(H₂O)₈ (5) and [Cu₃(HL2′)₄Cl₆](CH₃OH)₆ (6), as revealed by single-crystal X-ray studies. Their DNA-interacting abilities have been investigated using different characterization techniques, which suggest that the metal complexes act as efficient DNA binders. Moreover, cytotoxicity assays with several cancer cell lines show that some of them are very active, as evidenced by the sub-micromolar IC₅₀ values achieved in some cases.