Dithiocarbazate–FeIII, −CoIII, −NiII, and −ZnII Complexes: Design, Synthesis, Structure, and Anticancer Evaluation

Non-platinum-metal complexes show great potential as anticancer agents. Herein, a series of dithiocarbazate non-Pt-metal complexes, including [Fe^III(L)₂]·Cl·2H₂O 1, [Co^III(L)₂]·NO₃·2.5H₂O 2, [Ni^II(L)₂] 3, and [Zn^II(L)₂] 4, have been designed and evaluated for their efficacy as antineoplastic agents. Among them, complex 2 exhibited higher anticancer efficacy than complexes 1, 3, 4, and cisplatin against several cancer cell lines. Hemolysis assays revealed that complex 2 showed comparable hemolysis with cisplatin. In vivo anticancer evaluations showed that complex 2 could retard tumor xenograft growth effectively with low systemic toxicity. Further studies revealed that complex 2 suppressed cancer cells by triggering multiple mechanisms involving the simultaneous inhibition of mitochondria and glycolytic bioenergetics. Overall, our study provides new insights into the anticancer mechanism of Co complexes, which can be used as a good strategy to overcome the flexibility of cancer cells to chemotherapy adaptation.