DNA binding and antiproliferative activity toward human carcinoma cells of copper(ii) and zinc(ii) complexes of a 2,5-diphenyl[1,3,4]oxadiazole derivative

Abstract

The interaction of calf thymus DNA with [CuL(ClO₄)]ClO₄·H₂O (1) and [ZnLBr]Br·H₂O (2) (L = 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.0^2,7.0^20,25]enneicosa-2,4,6,20,22,24,26,28¹-octaene) dicationic complexes in aqueous solution at neutral pH, was investigated by variable-temperature UV-vis absorption, circular dichroism and fluorescence spectroscopy. The values of the DNA-binding constants of these complexes, determined by competitive binding spectrofluorimetric titrations of ethidium bromide (EB)–DNA solutions, are (6.7 ± 0.5) × 10⁶ M⁻¹ for CuL²⁺ and (4.7 ± 0.5) × 10⁵ M⁻¹ for ZnL²⁺. These data together with a through analysis of the spectroscopic behaviour consistently suggest that both compounds are effective DNA binders. Interestingly, the DNA-binding strength of these complexes has been found to be correlated to their in vitro cytotoxic activity toward human breast carcinoma cells, although the complex with lower DNA-binding affinity is more active. In fact, biological studies showed that when the compounds are delivered through the cell membrane by a lipidic carrier, the cell survival is sensibly reduced, up to 58% with 1 and to 31% with 2.