Inhibiting Erastin-Induced Ferroptotic Cell Death by Purine-Based Chelators.

Saurabh Joshi, Saloni Agarwal, Apurva Panjla, Suresh Valiyaveettil, Subramaniam Ganesh, Sandeep Verma

Chembiochem : a European journal of chemical biology 2022 May 04

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Ferroptosis is a cell death event caused by increased lipid peroxidation leading to iron-dependent oxidative stress and is associated with a wide variety of diseases. In recent years, ferroptosis inhibition has emerged as a novel strategy to target different pathologies. Here, we report the synthesis of two purine derivatives, 1 and 2, for iron chelation strategy and evaluate their potency to inhibit erastin-induced ferroptosis. Both compounds showed efficient iron chelation in solution as well as in cellular environment. The crystal structure of the purine derivatives with iron demonstrated a 2 : 1 (ligand to metal center) stoichiometry for iron and purine derivative complexation. The synthesized compounds also decrease the reactive oxygen species concentration in cell cultures. Compound 2 showed better potency towards the prevention of ferroptotic cell death as compared to commercially available iron chelator in the erastin-induced ferroptosis cell culture model. Such purine analogues are potential functional scaffolds for the development of target molecules for ferroptosis inhibition. © 2022 Wiley-VCH GmbH.

Citation

Saurabh Joshi, Saloni Agarwal, Apurva Panjla, Suresh Valiyaveettil, Subramaniam Ganesh, Sandeep Verma. Inhibiting Erastin-Induced Ferroptotic Cell Death by Purine-Based Chelators. Chembiochem : a European journal of chemical biology. 2022 May 04;23(9):e202100654