A Druglike Ferrostatin‐1 Analogue as a Ferroptosis Inhibitor and Photoluminescent Indicator
Redox-based diagnostic and therapeutic applications have long suffered from a shortage of suitable drugs and probes of high specificity. In the context of anti-ferroptosis research for neurological diseases, the inaccessibility of a blood-brain barrier (BBB) permeable small molecular ferroptosis inhibitor, and the lack of specific ferroptosis probes, seriously impeded a deeper understanding of the mechanism of ferroptosis and the development of clinically applicable drugs. We report herein a novel 1,3,4-thiadiazole-functionalized druglike ferrostatin analogue entitled Ferfluor-1 with superior anti-ferroptosis potency, favorable BBB permeability and in vivo activity against stroke and Parkinson's disease. Moreover, the exclusive pseudo-excited-state intramolecular proton-transfer (ESIPT) property of Ferfluor-1 via a long-distance hydrogen-bonding network makes it the first sensitive ratiometric photoluminescent probe to detect phospholipid hydroperoxides and a specific indicator for the fluctuation of ferroptosis. These unprecedented advantages not only make Ferfluor-1 a potential tool for ferroptosis-related diagnostic and therapeutic applications in the central nervous system, but also pave the way to developing new theragnostic agents for precision redox detection and regulation.
Authors
- Bo Chu (ORCID: https://orcid.org/0000-0001-9754-2743)
- Lingfeng Kong (ORCID: https://orcid.org/0000-0001-5263-1697)
- K H Wang
- Xue Qiu (ORCID: https://orcid.org/0000-0003-0635-6801)
- Jiangkun Yan
- Michael J. McGlinchey (ORCID: https://orcid.org/0000-0002-4342-0166)
- Xinyu Han (ORCID: https://orcid.org/0000-0003-1031-652X)
- Weidong Sun (ORCID: https://orcid.org/0000-0001-8718-1710)
- Chuanbin Shen (ORCID: https://orcid.org/0000-0002-4635-5160)
- Yong Wang (ORCID: https://orcid.org/0000-0003-3222-0211)
- Xuejing Fan
- Min Liu (ORCID: https://orcid.org/0000-0001-5183-1187)
- Tongtong Liu (ORCID: https://orcid.org/0009-0004-3694-5011)
- Huicong Liang
- Chunhui Liang (ORCID: https://orcid.org/0000-0002-0476-2286)
- Ximing Xu (ORCID: https://orcid.org/0000-0002-2125-7345)
- Xin J. Zhou (ORCID: https://orcid.org/0000-0002-1617-334X)
- Zhao Li (ORCID: https://orcid.org/0000-0001-5475-0809)
- Luo Bao
Institutions
- University College Dublin (IE)
- Qingdao University (CN)
- Shandong University (CN)
- Jinan University (CN)
- Qingdao National Laboratory for Marine Science and Technology (CN)
- China University of Petroleum, East China (CN)
- Shandong First Medical University (CN)
- Ocean University of China (CN)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-02-21
- DOI
- https://doi.org/10.1002/anie.202502195
- Citations
- 19
- Primary Topic
- Metal complexes synthesis and properties
- Type
- article
- Field-Weighted Citation Impact
- 19.86
Funders
- National Natural Science Foundation of China
- Ocean University of China
- Natural Science Foundation of Shandong Province
- Fundamental Research Funds for the Central Universities