Pyrene aroylhydrazone-based Pd(II) complexes for DNA/protein binding, cellular imaging and in vitro anticancer activity via ROS production

A novel class of Pd(II) pyrene aroylhydrazone complexes (Pd1-Pd4) of general formula [Pd(L)(PPh3)Cl] (L=pyrene aroylhydrazones) was synthesized and their solid-state structures were determined by single-crystal XRD study. In vitro cytotoxicity of Pd1-Pd4 were examined against two cancer cell lines, HeLa and MCF-7 and two non-cancerous cell line, HEK 293T and 3T3-L1 to assess their selectivity. Among these, Pd2 and Pd3 had the most significant cytotoxic effects in comparison to cisplatin, a traditional anticancer medication featuring undesirable side effects, in tested cancer cell lines. Moreover, they showed noticeably less toxicity towards non-cancerous cell lines. Their interactions with serum albumin were confirmed experimentally as well as with molecular docking. Pd3 was also found to effectively interact with DNA as revealed by DNA interactions studies. Pd3-treated HeLa cells exhibited nuclear apoptotic features such as chromatin condensation and nuclear fragmentation and was also found to induce ROS which further led to decrease in mitochondrial membrane potential in cancer cells. Further, Pd3 was efficiently internalized by HeLa cells as evident from cellular imaging using confocal microscopy. Taken together, we report a novel class of Pd(II) pyrene aroylhydrazone complexes displaying strong protein/DNA binding and anti-cancer activity via ROS generation under in vitro circumstances.