Vol.:(0123456789) 1 3 JBIC Journal of Biological Inorganic Chemistry https://doi.org/10.1007/s00775-019-01653-6 ORIGINAL PAPER 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 Büşra Kaya 1  · Zehra Kübra Yılmaz 2  · Onur Şahin 3  · Belma Aslim 2  · Ümmügülsüm Tükenmez 4  · Bahri Ülküseven 1 Received: 21 January 2019 / Accepted: 13 March 2019 © Society for Biological Inorganic Chemistry (SBIC) 2019 Abstract 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 adenocar- cinoma (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 signifcant 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 afnities. Cytotoxicity determination tests revealed that the complex Fe1 on HeLa and HT-29 cells exhibited a higher anti- proliferative efect 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. Graphical abstract Keywords Thiosemicarbazone · Iron · Manganese · DNA binding · DNA cleavage · Anti-proliferation Introduction Biologically functional molecules are one of the top prefer- ential topics in chemistry research. In drug development pro- cesses, efective chemicals targeting especially the treatment Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00775-019-01653-6) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article