Ferroptosis Mediated Novel Drug Design Approach in the Treatment of Oral Squamous Cell Carcinoma.

Background: Globally, Oral Squamous Cell Carcinoma (OSCC) is the highest prevalent type of oral cancer. Implementing a successful treatment plan for the aforementioned tumor has always been a primary concern. There are numerous targeted therapies of which Ferroptosis has been receiving increasing attention in the recent decade. A novel form of controlled cell death "Ferroptosis' is caused by iron-dependent lipid peroxidation. A well-known mechanism for controlling ferroptosis is the Cysteine/GSH/GPX4 axis, in which System X͞c is crucial. System X͞c inhibitors have been proven earlier to improve chemotherapy sensitivity.

Materials And Methods: Five System X͞c inhibitors were selected from the literature. The structure of these molecules from Zinc15 and the protein sequence of the target from Protein Data Bank were obtained. Twenty new molecules were identified following pharmacophore modeling and were docked with the target protein using SwissDock. The binding energies of the new molecules with the target were compared with that of the reported molecules.

Result: The molecular docking study showed that two new molecules (ZINC89362298 and ZINC1730544) resulted in the highest binding pattern (-8.64) than that of the reported molecules (-7.75).

Conclusion: The present study concluded that ZINC89362298 and ZINC1730544 had better binding efficiencies than that of the reported System xc- inhibitors. Hence these two molecules could be used in targeted drug therapy and could be a promising lead in the management of oral cancer in the future.