Detailed profiling on DNA binding affinity, cytotoxicity and pathway of induced cell death of novel water-soluble Cu(II)-based acylhydrazone porphyrin derivatives

摘要

A panel of novel water-soluble Cu(II)-based acylhydrazone porphyrin complexes (denoted as Cu-PorX, X = 1, 2 and 3. See Fig. 1) were prepared and characterized. Versatile physicochemical approaches indicated that whole compounds could effectively bind with ct-DNA through intercalative or intercalative coupled with end-stacking interaction, especially, Cu-Por3 has the strongest binding affinity compared with others. Additionally, the antiproliferative activity has been evaluated by MTT assay turned out that Cu-Por3 yet exhibits gratifying cytotoxicity towards A549 (non-small cell lung cancer) cell line, suggesting that Cu-Por3 is a potential candidacy among tested agents. We also carried out the cellular uptake measurement by using an extracted method to better comprehend the anticancer behaviors. Moreover, for gaining deeper insight into the mechanism of cell death of affected by the representative complex Cu-Por3, the influences of this new conjugate on the cell cycle and the induction of apoptosis were illustrated via employing flow cytometric analysis. (C) 2016 Elsevier Ltd. All rights reserved.