Exploiting Co(III)-Cyclopentadienyl Complexes To Develop Anticancer Agents

João Franco Machado, Sandra Cordeiro, Joana N. Duarte, Paulo J. Costa, Paulo J. Mendes, Maria Helena Garcia, Pedro V. Baptista, Alexandra R. Fernandes, Tânia S. Morais

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Abstract

In recent years, organometallic complexes have attracted much attention as anticancer therapeutics aiming at overcoming the limitations of platinum drugs that are currently marketed. Still, the development of half-sandwich organometallic cobalt complexes remains scarcely explored. Four new cobalt(III)-cyclopentadienyl complexes containing N,N-heteroaromatic bidentate, and phosphane ligands were synthesized and fully characterized by elemental analysis, spectroscopic techniques, and DFT methods. The cytotoxicity of all complexes was determined in vitro by the MTS assay in colorectal (HCT116), ovarian (A2780), and breast (MDA-MB-231 and MCF-7) human cancer cell lines and in a healthy human cell line (fibroblasts). The complexes showed high cytotoxicity in cancer cell lines, mostly due to ROS production, apoptosis, autophagy induction, and disruption of the mitochondrial membrane. Also, these complexes were shown to be nontoxic in vivo in an ex ovo chick embryo yolk sac membrane (YSM) assay.
Original languageEnglish
Pages (from-to)5783-5804
Number of pages22
JournalInorganic Chemistry
Volume63
Issue number13
DOIs
Publication statusPublished - 1 Apr 2024

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