Dithiocarbazate-Copper Complexes for Bioimaging and Treatment of Pancreatic Cancer

  • J Med Chem. 2021 May 13;64(9):5485-5499. doi: 10.1021/acs.jmedchem.0c01936.
Yi Gou  1 ,  MeiRong Chen  1 ,  Shanhe Li  2 ,  JunGang Deng  1 ,  Jinlong Li  3 ,  GuiHua Fang  3 ,  Feng Yang  2 ,  GuoJin Huang  1
Affiliations
  • 1. Laboratory of Respiratory Disease, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, China.
  • 2. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin 541004, Guangxi, China.
  • 3. School of Pharmacy, Nantong University, Nantong 226019, Jiangsu, China.
PMID: 33861929 DOI: 10.1021/acs.jmedchem.0c01936
Abstract

Anticancer agents that present nonapoptotic cell death pathways are required for treating apoptosis-resistant pancreatic Cancer. Here, we synthesized three fluorescent dithiocarbazate-copper complexes, {[CuII(L)(Cl)] 1, [CuII2(L)2(NO3)2] 2, and [CuII2CuI(L)2(Br)3] 3}, to assess their antipancreatic Cancer activities. Complexes 1-3 showed significantly greater cytotoxicity toward several pancreatic Cancer cell lines with better IC50 than those of the HL ligand and cisplatin. Confocal fluorescence imaging showed that complex 3 was primarily localized in the mitochondria. Primarily, compound 3 also can be applied to in vivo imaging. Further studies revealed that complex 3 kills pancreatic Cancer cells by triggering multiple mechanisms, including Ferroptosis. Complex 3 is the first copper complex to evoke cellular events consistent with Ferroptosis in Cancer cells. Finally, it significantly retarded the ASPC-1 cells' growth in a mouse xenograft model.

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