DNA binding and in vitro antineoplastic activity of neotype water-soluble Cu(II)-complexes based on fluorinated benzoylhydrazone porphyrin ligands

Abstract Three water-soluble Cu(Ⅱ)-based acylhydrazone porphyrin derivatives (named as CuP1 , CuP2 and CuP3 ) were prepared and isolated successfully. Diversiform physicochemical approaches demonstrated that all of the complexes possess excellent binding affinity with ct-DNA, especially CuP3 exhibited strongest binding affinity than its analogues. Moreover, the antiproliferative properties of all compounds in vitro in human cancer cell line (A549 and H-1975 lung cancer cells, HepG2 human hepatocarcinoma, T47D breast cancer cells) and noncancerous cell line (Hs 578Bst normal breast cells) have also been evaluated by MTT assay. Besides, an extracted method was carried out to determine the cellular uptake ability of three complexes to the tested cancer cell lines. The cytotoxicity and cellular uptake tests revealed that CuP3 exhibited the best antiproliferative activity as well as cellular absorption capacity towards H-1975 cell line. In order to better understand the effects of CuP3 on H-1975 cells, the fluorescence microscopy measurements were employed, the cell membrane damage, nuclear condensation, and apoptotic bodies (brighter fluorescence) were markedly observed after incubated with CuP3 for 48 h, suggesting that CuP3 can induce cell apoptosis on H-1975 cells significantly. In addition, the flow cytometric analysis results illustrated that the complex CuP3 mainly caused an accumulation of cells in the G2 phase of the cell cycle.