Structural analysis and biological functionalities of iron(III)- and manganese(III)-thiosemicarbazone complexes: in vitro anti-proliferative activity on human cancer cells, DNA binding and cleavage studies.

One iron(III) and two manganese(III) complexes based on thiosemicarbazone were synthesized and characterized using analytical and spectroscopic data. The crystallographic analysis showed the square pyramid structures of the complexes. Electronic spectra analysis was performed to determine the nature of the interaction between the complexes and calf thymus DNA (CT-DNA). DNA cleavage activities of the complexes were examined by gel electrophoresis (pBR322 DNA). The cytotoxicity of the complexes was determined against human cervical carcinoma (HeLa) and human colorectal adenocarcinoma (HT-29) cell lines by MTT assay. The results indicated that complex Fe1 is bound to CT-DNA via the intercalation mode, while complexes Mn1 and Mn2 are bound to CT-DNA via groove binding and/or electrostatic interactions rather than the intercalation mode. In addition, they showed good binding activity, which followed the order of Fe1 > Mn2 > Mn1. Complexes were found to promote the cleavage of DNA from supercoiled form (SC, Form I) to nicked circular form (NC, Form II) without concurrent formation of Form III, revealing the single-strand DNA cleavage. No significant cleavage was found in the presence of Mn1 and Mn2; however, it was observed at 2000 and 3000 µM concentrations of Fe1. The ability of Fe1 to cleave DNA was greater than that of other complexes and these results are in conformity with their DNA-binding affinities. Cytotoxicity determination tests revealed that the complex Fe1 on HeLa and HT-29 cells exhibited a higher anti-proliferative effect than Mn1 and Mn2 (Fe1 > Mn2 > Mn1). These studies suggested that the complex Fe1 could be a good candidate as a chemotherapeutic drug targeting DNA.

A new bio-active asymmetric-Schiff base: synthesis and evaluation of calf thymus DNA interaction, topoisomerase IIα inhibition, in vitro antiproliferative activity, SEM analysis and molecular docking studies.

In this paper, the asymmetric-Schiff base 2-(4-(2-hydroxybenzylideneamino)benzylideneamino)benzoic acid (SB-2) was newly synthesized and characterized by various spectroscopic methods. The interaction of SB-2 with calf thymus DNA was investigated by UV-vis, fluorescence spectroscopy and molecular docking methods. It was determined that SB-2 effectively binds to DNA via the intercalation mode. DNA electrophoretic mobility experiments displayed that topoisomerase IIα could not cleave pBR322 plasmid DNA in the presence of SB-2, confirming that the Schiff base acts as a topo II suppressor. In the molecular docking studies, SB-2 was found to show an affinity for both the DNA-topoisomerase IIα complex and the DNA. In vitro antiproliferative activity of SB-2 was screened against HT-29 (colorectal) and HeLa (cervical) human tumor cell lines by MTT assay. SB-2 diminished the cell viability in a concentration- and incubation time-dependent manner. The ability of SB-2 to measure DNA damage in tumor cells was evaluated with cytokinesis-block micronucleus assay after incubation 24 h and 48 h. Light and scanning electron microscopy experiments of tumor cells demonstrated an incubation time-dependent increase in the proportion of apoptotic cells (nuclear condensation and apoptotic bodies) suggesting that autophagy and apoptosis play a role in the death of cells. Based on the obtained results, it may be considered that SB-2 is a candidate for DNA-targeting antitumor drug.Communicated by Ramaswamy H. Sarma.