An experimental and theoretical approach of coordination compounds derived from meso-tetra(thiophen-2-yl)porphyrin: DNA interactions and cytotoxicity

Abstract

In this work meso-tetra(thiophen-2-yl)-porphyrin and their metal complexes of zinc(II), nickel(II), cobalt(II), copper(II), and manganese(III) were synthesized. The compounds were characterized by 1H NMR, HRMS-ESI, elemental analysis, theoretical and experimental spectroscopic studies in the infrared and UV–visible regions. Furthermore, the electronic nature of the complexes was described by reactivity parameters, such as softness, hardness, chemical potential, electrophilicity index, and NBO charges. The complexes were submitted to the DMSO stability and lipophilicity test, essentials for the biomolecular and biological assays. The interactions with DNA were performed with ct-DNA for spectrophotometric titration and pBR322 plasmid in agarose gel electrophoresis. All complexes have a weak interaction with ct-DNA, although the MnPCl complex was the more active. In cytotoxicity assay, the complexes were screened against the tumor cell lines DU-145 (prostate cancer), A549 (lung cancer), and A2780cis (cisplatin-resistant ovarian cancer) and a lung non-tumor cell line (MRC-5) via MTT assay. Only the MnPCl complex was active on all cell lines with values IC50 ranges 1.52–3.45 μM and exhibited higher cytotoxicity than cisplatin (control drug). The porphyrin compounds do not have a significant difference in DNA interaction, which explains the difference in the IC50. The MnPCl has another target or cell role that provides a small IC50 compared to the analog compounds.