Pd(II) complexes with N-heteroaromatic hydrazones as dual targeting DNA/Topoisomerase 1 agents: experimental and in silico study

Abstract

Anticancer activity of five Pd(II) pyridine-based hydrazone complexes (1‒5, Figure 1) was investigated against a human monocytic leukemia THP-1 (2D) cell line and a breast cancer MCF-7 (2D and 3D) cell line. For complexes with apoptosis as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce ROS and in vitro inhibit topoisomerase I in a low micromolar range. In silico studies corroborate experimental findings and indicate binding to DNA's minor groove. The most active compounds are suitable to be transported via blood stream by human serum albumin, as results of CD and fluorescence spectroscopy showed.