Organometallic Gold(III) Complexes Similar to Tetrahydroisoquinoline (THIQ) Induce ER-stress-mediated Apoptosis and Pro-death Autophagy in A549 Cancer Cells.

Research paper by Ke-Bin KB Huang, Feng-Yang FY Wang, Xiao-Ming XM Tang, Hai-Wen HW Feng, Zhen-Feng ZF Chen, Yan-Cheng YC Liu, You-Nian YN Liu, Hong H Liang

Indexed on: 03 Apr '18Published on: 03 Apr '18Published in: Journal of Medicinal Chemistry


Agents induced both apoptosis and autophagic death can be effective chemotherapeutic drugs. In our present work, we synthesized two organometallic gold(III) complexes harbouring C^N ligands that structurally resemble THIQ, Cyc-Au-1 (AuL1Cl2, L1 = 3,4-dimethoxyphenethylamine) and Cyc-Au-2 (AuL2Cl2, L2 = methylenedioxyphenethylamine). In screening their in vitro activity, we found both gold complexes to exhibit lower toxicity, lower resistance factors and better anticancer activity than cisplatin. The organometallic gold(III) complexes accumulate in mitochondria and induce elevated ROS and an ER stress response through mitochondrial dysfunction. These effects ultimately result in simultaneous apoptosis and autophagy. Importantly, compared to cisplatin, Cyc-Au-2 exhibits lower toxicity and better anticancer activity in a murine tumor model. To the best of our knowledge, Cyc-Au-2 is the first organometallic Au(III) compound that induces apoptosis and autophagic death. Based on our results, we believe Cyc-Au-2 to be a promising anticancer agent or lead compound for further anticancer drug development.