Redox modulator iron complexes trigger intrinsic apoptosis pathway in cancer cells.

The emergence of multidrug resistance in cancer cells necessitates the development of new therapeutic modalities. One way cancer cells orchestrate energy metabolism and redox homeostasis is through overloaded iron pools directed by iron regulatory proteins, including transferrin. Here, we demonstrate that targeting redox homeostasis using nitrogen-based heterocyclic iron chelators and their iron complexes efficiently prevents the proliferation of liver cancer cells (EC: 340 nM for IITK4003) and liver cancer 3D spheroids.

Diazepam-based covalent modifiers of GPX4 induce ferroptosis in liver cancer cells.

Developing new chemotherapeutics that are structurally and mechanistically unique is needed due to the rapid rise of the cancer incidence across the globe. Here, we report the identification of irreversible, thiol-reactive diazepam derivatives as GPX4 modifiers and nanomolar inducers of ferroptosis in liver cancer cells.

Mn(II) Polypyridyl Complexes: Precursors to High Valent Mn(V)=O Species and Inhibitors of Cancer Cell Proliferation.

The reaction of [(L)Mn ] (L = neutral polypyridine ligand framework) in the presence of mCPBA (mCPBA = m-Chloroperoxybenzoic acid) generates a putative Mn =O species at RT. The proposed Mn =O species is capable of performing the aromatic hydroxylation of Cl-benzoic acid derived from mCPBA to give [(L)Mn (m-Cl-salicylate)] which in the presence of excess mCPBA generates a metastable [(L)Mn (O)(m-Cl-salicylate)] , characterized by UV/Vis absorption, EPR, resonance Raman spectroscopy, and ESI-MS studies. The current study highlights the fact that [(L)Mn (m-Cl-salicylate)] formation may not be a dead end for catalysis.