An alpha-lipoic acid phenothiazine derivative, and a preparation method and application thereof
By designing α-lipoic acid phenothiazine derivatives and utilizing the synergistic effect of the tricyclic phenothiazine skeleton and R group, the problem of insufficient anti-ferroptosis efficacy of α-lipoic acid was solved, achieving highly efficient and low-toxicity anti-ferroptosis and anti-inflammatory effects, and significantly improving the activity and safety of ferroptosis inhibitors.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- YANAN UNIV
- Filing Date
- 2025-10-15
- Publication Date
- 2026-06-16
AI Technical Summary
Although the existing natural product alpha-lipoic acid has both anti-ferroptosis and anti-inflammatory effects, its anti-ferroptosis efficacy is insufficient and it causes severe inflammatory reactions.
An α-lipoic acid phenothiazine derivative was designed. Through the synergistic effect of the unique tricyclic phenothiazine skeleton and the α-lipoic acid moiety, and by introducing R groups such as Boc-aminocycloalkyl acids, the drug's transmembrane transport and targeting of mitochondria are enhanced, non-specific toxicity is reduced, and highly efficient anti-ferroptosis and anti-inflammatory effects are achieved.
This derivative significantly enhances anti-ferroptosis activity, with an EC50 of 2.5 nM, which is 15,000 times stronger than α-lipoic acid. It also has low toxicity and good anti-inflammatory activity, effectively protecting cells from ferroptosis and inflammatory damage.