Copper(II) Complexes of Pyrazolopyrimidine Derivatives as Anticancer Agents with Enhanced Chemodynamic Therapy through Bimodal Apoptosis and Ferroptosis
Kun Yang, Qian Chen, Juan Chen, Li Geng, Meng‐Xue Ma, Yun‐Qiong Gu, M. Iqbal Choudhary, Hong Liang, Zhen‐Feng Chen
Abstract
We reported 10 new copper(II) complexes 1 – 10 with pyrazolopyrimidine derivatives as ligands. Complexes 2 and 4 reacted with glutathione (GSH) in cells through Fenton-like reaction to generate highly toxic hydroxyl radical (·OH) for chemodynamic therapy (CDT), and reduced endogenous glutathione peroxidase 4 (GPX4) to induce ferroptosis. In addition, these complexes effectively caused mitochondrial dysfunction and induced apoptosis and autophagy in tumor cells. Furthermore, 2 and 4 effectively inhibited the bladder cancer cell growth in a xenograft model. This study presents new copper(II) complexes that can significantly induce bladder cancer cells death by enhanced CDT through bimodal apoptosis and ferroptosis, providing a promising approach for cancer therapy.