CETZOLE Analogs as Potent Ferroptosis Inducers and Their Target Identification Using Covalent/Affinity Probes.

ABSTRACT: Ferroptosis is a recently discovered cell death mechanism triggered by iron-dependent elevation of reactive oxygen species leading to lipid membrane peroxidation. We previously reported the development of a new class of ferroptosis inducers referred to as CETZOLEs with CC₅₀ values in the low micromolar range. Structure-activity relationship study of these compounds led to the development of more potent analogs with CC₅₀ values in the nanomolar range. Cells exposed to these compounds displayed the hallmarks of ferroptosis including cell death through ROS accumulation. Cancer cells were found to be more sensitive to these compounds than normal cells. Proteomic studies using covalent and affinity probes led to the identification of cystathionine β-synthase, peroxiredoxin

SUBMITTER: Dlamini S 

PROVIDER: S-EPMC12338762 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature