Investigation of novel Mn(ii) fenamato complexes with neocuproine and their effects on endometrial cell lines

Abstract

Two novel Mn(II) complexes with non-steroidal anti-inflammatory drugs, fenamic (Hfen = 2-(phenylamino)benzoic acid) and flufenamic acid (Hflu = N-(3-trifluoromethylphenyl)-2-aminobenzoic acid) and neocuproine (neo) as a supporting ligand were designed, synthesized and characterized. Their molecular structure was determined by the single-crystal X-ray diffraction method, which revealed that the complexes are isostructural and form analogous molecules [Mn(neo)(fen)₂] and [Mn(neo)(flu)₂]. Both complexes create an interesting structural motif resembling molecular tweezers, with an open cavity between the fenamato and flufenamato ligands, and exhibit moderate radical scavenging activity, with the fenamato complex being more active. The cytotoxic effects of the complexes were studied on three selected cell lines, including epithelial hTERT HME1 used as a healthy control, endometriotic 12Z and endometrial cancer SK-UT-1. The complexes were most active against the 12Z among the studied cell lines, while the flufenamato complex, which showed an IC₅₀ value around 2 μM, was able to effectively trigger apoptosis through the caspase pathway. The impact of the complexes on the expression of selected genes in the tested cell lines was further investigated by qRT-PCR methods and their DNA binding properties towards the isolated genomic DNA samples were evaluated by competitive binding studies with ethidium bromide. Although some differences in the biological activity of the complexes were found, it can be concluded that both complexes target the inflammatory processes on a cellular level.