What question did this study set out to answer?

The research aims to explore the synthesis of diphyllin derivatives and their potential for inducing ferroptosis in cancer cells.

February 8, 2026

Thioether and ether derivatives of diphyllin: synthesis and inducing tumor ferroptosis activity

Key Points

The research aims to explore the synthesis of diphyllin derivatives and their potential for inducing ferroptosis in cancer cells.
Synthesis of diphyllin thioether and ether derivatives via epoxide nucleophilic ring-opening reaction
Assessment of cytotoxic activity against HepG2, HCT-15, and A549 cancer cell lines
Evaluation of antitumor mechanisms focusing on GPX4 expression inhibition
Compound 3a demonstrated the highest cytotoxicity with IC50 values from 0.03 to 0.63 µM
Thioether derivative 3a selectively inhibits glutathione peroxidase GPX4 expression
Induction of ferroptosis was confirmed in A549 cells.

Abstract

A series of nine diphyllin thioether and four ether derivatives were designed and successfully synthesised via epoxide nucleophilic ring-opening reaction. These compounds demonstrated pronounced cytotoxic activity against the human cancer cell lines HepG2, HCT-15, and A549. Notably, thioether derivative 3a exhibited the most potent cytotoxicity, with IC50 values ranging from 0.03 to 0.63 µM. Research on the antitumor mechanism revealed that compound 3a selectively inhibits the expression of glutathione peroxidase GPX4, inducing ferroptosis in A549 cells.

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Cite This Study

Han et al. (Thu,) studied this question.

synapsesocial.com/papers/698827670fc35cd7a88461f2 https://doi.org/https://doi.org/10.1080/14786419.2026.2624785

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