Synthesis and characterization of novel palladium(II) complexes of bis(thiosemicarbazone). Structure, cytotoxic activity and DNA binding of Pd(II)-benzyl bis(thiosemicarbazonate)

Abstract

The preparation of palladium(II) complexes of 3,5-diacyl-1,2,4-triazole bis(thiosemicarbazone) (H 2L 2), 2,6-diacylpyridine bis(thiosemicarbazone) (H 2L 3) and benzyl bis(thiosemicarbazone) (H 2L 4) is described. The new complexes [PdCl 2(H 2L 2)] ( 1), [PdCl 2(H 2L 3)] ( 2) and [PdL 4] ·DMF ( 3) have been characterized by elemental analyses and spectroscopic studies (IR, 1H NMR and UV–Vis). The crystal and molecular structure of PdL 4 ·DMF (L=bideprotonated form of benzyl bis(thiosemicarbazone)) has been determined by single-crystal X-ray diffraction: green triclinic crystal, a=10.258(5), b=10.595(5), c=11.189(5) Å, α=97.820(5), β=108.140(5), γ=105.283(5)°, space group P1, Z=1. The palladium atom is tetracoordinated by four donor atoms (SNNS) from L 4 to form a planar tricyclic ligating system. The testing of the cytotoxic activity of compound 3 against several human, monkey and murine cell lines sensitive (HeLa, Vero and Pam 212) and resistant to cis-DDP (Pam- ras) suggests that compound 3 might be endowed with important antitumor properties since it shows IC 50 values in a μM range similar to those of cis-DDP [ cis-diamminedichloroplatinum (II)]. Moreover, compound 3 displays notable cytotoxic activity in Pam- ras cells resistant to cis-DDP (IC 50 values of 78 μM versus 156 μM, respectively). On the other hand, the analysis of the interaction of this novel Pd-thiosemicarbazone compound with DNA secondary structure by means of circular dichroism spectroscopy indicates that it induces on the double helix conformational changes different from those induced by cis-DDP.