Structural characterization of new zinc(ii) complexes with N2O2 chelating thiosemicarbazidato ligands; investigation of the relationship between their DNA interaction and in vitro antiproliferative activity towards human cancer cells

Abstract

Two new zinc(ii) complexes were synthesized by condensation of 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione-S-methyl-thiosemicarbazone with salicylaldehyde or 4-methoxy-salicylaldehyde. Structures of the N2O2-chelate complexes, Zn1 and Zn2, were explicated by IR, H-1 NMR, ESI-MS and X-ray crystallography. Electronic spectral analysis was performed to assign the nature of the interaction between the complexes and calf thymus DNA (CT-DNA). DNA cleavage activities of the complexes were investigated by gel electrophoresis (pBR322 DNA). The results indicated that the complexes bind to CT-DNA via an intercalation mode and the binding of Zn2 is stronger than that of Zn1. Relatively high concentrations of the zinc complexes were found to encourage the cleavage of DNA from supercoiled form (Form I) to nicked circular form (Form II). The antiproliferative activity of the complexes was determined against human colorectal adenocarcinoma (HT-29) and human cervical carcinoma (HeLa) cell lines by MTT assay. The tests revealed that the complex Zn2 exhibited a higher antiproliferative effect than Zn1 on HT-29 and HeLa cells, analogical to the data from DNA interaction experiments. The studies demonstrated that complex Zn2 could be a good candidate as a chemotherapeutic drug targeting DNA.