Novel water-soluble Cu(II) complexes based on acylhydrazone porphyrin ligands for DNA binding and in vitro anticancer activity as potential therapeutic targeting candidates.

Three novel water-soluble Cu(II) complexes featuring miscellaneous acylhydrazone tricationic porphyrin ligands (named as Cu-Por1, Cu-Por2 and Cu-Por3) were successfully prepared and isolated. Numerous physicochemical techniques demonstrated that all the complexes exhibited favourable binding properties with calf thymus DNA (ct-DNA), especially Cu-Por3, which had a stronger binding affinity compared with other analogues. In addition, the antiproliferative activity of the three complexes has been evaluated using MTT assay, suggesting excellent cytotoxicity for A549, H-1975, HepG2, and T47D tumor cell lines, and little toxicity for Hs 578Bst normal breast cancer cells due to the specific targeting of porphyrins. The extraction method was also used to determine the cell uptake capacity of the three complexes on the tested cancer cell lines. At the same time, fluorescence microscopy analysis demonstrated that Cu-Por1 and Cu-Por3 could promote the apoptosis of H-1975 or HepG2 cells with shrunken or fragmented nuclei cells. Moreover, flow cytometry experiments further confirmed the excellent anti-tumor activity of these types of porphyrin derivatives. Our findings disclosed that this type of porphyrin complex would represent a powerful platform for the development of novel and useful metal anticancer drugs. [ABSTRACT FROM AUTHOR]