Iron Chelator Transmetalative Approach to Inhibit Human Ribonucleotide Reductase.

ABSTRACT: Efforts directed at curtailing the bioavailability of intracellular iron could lead to the development of broad-spectrum anticancer drugs given the metal's role in cancer proliferation and metastasis. Human ribonucleotide reductase (RNR), the key enzyme responsible for synthesizing the building blocks of DNA replication and repair, depends on Fe binding at its R2 subunit to activate the catalytic R1 subunit. This work explores an intracellular iron chelator transmetalative approach to inhibit RNR using the titanium(IV) chemical transferrin mimetic (cTfm) compounds Ti(HBED) and Ti(Deferasirox)₂. Whole-cell EPR studies reveal that the compounds can effectively attenuate RNR activity though seemingly causing different changes to the labile iron pool that may account for differences

SUBMITTER: Gaur K 

PROVIDER: S-EPMC8243325 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature