| New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis | |
Feng, Wenya; Xiao, Yuanjing; Zhao, Chuanfang; Zhang, Zhanming; Liu, Wei ; Ma, Juan; Ganz, Tomas; Zhang, Junliang; Liu, Sijin
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| 2022-08-26 | |
| Source Publication | ADVANCED SCIENCE
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| Issue | 0Pages:2202679 |
| Abstract | Excess iron accumulation occurs in organs of patients with certain genetic disorders or after repeated transfusions. No physiological mechanism is available to excrete excess iron and iron overload to promote lipid peroxidation to induce ferroptosis, thus iron chelation becomes critical for preventing ion toxicity in these patients. To date, several iron chelators have been approved for iron chelation therapy, such as deferiprone and deferoxamine, but the current iron chelators suffer from significant limitations. In this context, new agents are continuously sought. Here, a library of new deferric amine compounds (DFAs) with adjustable skeleton and flexibility is synthesized by adopting the beneficial properties of conventional chelators. After careful evaluations, compound DFA1 is found to have greater efficacy in binding iron through two molecular oxygens in the phenolic hydroxyl group and the nitrogen atom in the amine with a 2:1 stoichiometry. This compound remarkably ameliorates iron overload in diverse murine models through both oral and intravenous administration, including hemochromatosis, high iron diet-induced, and iron dextran-stimulated iron accumulation. Strikingly, this compound is found to suppress iron-induced ferroptosis by modulating the intracellular signaling that drives lipid peroxidation. This study opens a new approach for the development of iron chelators to treat iron overload. |
| Department | 环境化学与生态毒理学国家重点实验室 ; 环境化学与生态毒理学国家重点实验室 |
| Keyword | HEREDITARY HEMOCHROMATOSIS MEDICAL PROGRESS DEFERIPRONE L1 BASIS-SET DISEASE HFE DEFEROXAMINE CONSEQUENCES THALASSEMIA METABOLISM |
| Document Type | 期刊论文 |
| Identifier | https://ir.rcees.ac.cn/handle/311016/47584 |
| Collection | 环境化学与生态毒理学国家重点实验室 |
| Affiliation | 1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.East China Normal Univ, Sch Chem & Mol Engn, 500 Dongchuan Rd, Shanghai 200241, Peoples R China 4.Fudan Univ, Dept Chem, 2005 Songhu Rd, Shanghai 200438, Peoples R China 5.Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA |
| Recommended Citation GB/T 7714 | Feng, Wenya,Xiao, Yuanjing,Zhao, Chuanfang,et al. New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis[J]. ADVANCED SCIENCE,2022(0):2202679. |
| APA | Feng, Wenya.,Xiao, Yuanjing.,Zhao, Chuanfang.,Zhang, Zhanming.,Liu, Wei.,...&Liu, Sijin.(2022).New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis.ADVANCED SCIENCE(0),2202679. |
| MLA | Feng, Wenya,et al."New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis".ADVANCED SCIENCE .0(2022):2202679. |
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| New Deferric Amine C（4436KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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