Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus.
Int J Mol Sci. 2021 May 24;22(11):5546. doi: 10.3390/ijms22115546.
The trimaltol iron complex (International Non-proprietary Name: ferric maltol) was originally designed, synthesised, and screened in vitro and in vivo in 1980-1981 by Kontoghiorghes G.J. following his discovery of the novel alpha-ketohydroxyheteroaromatic (KHP) class of iron chelators (1978-1981), which were intended for clinical use, including the treatment of iron deficiency anaemia (IDA). Iron deficiency anaemia is a global health problem affecting about one-third of the world's population. Many (and different) ferrous and ferric iron complex formulations are widely available and sold worldwide over the counter for the treatment of IDA. Almost all such complexes suffer from instability in the acidic environment of the stomach and competition from other dietary molecules or drugs. Natural and synthetic lipophilic KHP chelators, including maltol, have been shown in in vitro and in vivo studies to form stable iron complexes, to transfer iron across cell membranes, and to increase iron absorption in animals. Trimaltol iron, sold as Feraccru or Accrufer, was recently approved for clinical use in IDA patients in many countries, including the USA and in EU countries, and was shown to be effective and safe, with a better therapeutic index in comparison to other iron formulations. Similar properties of increased iron absorption were also shown by lipophilic iron complexes of 8-hydroxyquinoline, tropolone, 2-hydroxy-4-methoxypyridine-1-oxide, and related analogues. The interactions of the KHP iron complexes with natural chelators, drugs, metal ions, proteins, and other molecules appear to affect the pharmacological and metabolic effects of both iron and the KHP chelators. A new era in the treatment of IDA and other possible clinical applications, such as theranostic and anticancer formulations and metal radiotracers in diagnostic medicine, are envisaged from the introduction of maltol, KHP, and similar lipophilic chelators.
三羟甲基麦芽酚铁复合物（国际非专利名称：ferric maltol）最初是由 Kontoghiorghes G.J. 在 1980 年至 1981 年间设计、合成和筛选的，当时他发现了新型的α-酮羟基杂芳族（KHP）类铁螯合剂（1978-1981 年），这些螯合剂旨在用于临床，包括治疗缺铁性贫血（IDA）。缺铁性贫血是一个全球性的健康问题，影响着全球约三分之一的人口。许多（不同的）亚铁和高铁铁复合物制剂在全球范围内以非处方形式广泛销售，用于治疗 IDA。几乎所有这些复合物在胃的酸性环境中都不稳定，并且会受到其他膳食分子或药物的竞争。在体内和体外研究中，天然和合成的亲脂性 KHP 螯合剂，包括麦芽酚，已被证明可以形成稳定的铁复合物，跨细胞膜转运铁，并增加动物的铁吸收。三羟甲基麦芽酚铁，以 Feraccru 或 Accrufer 的形式出售，最近在包括美国和欧盟国家在内的许多国家被批准用于 IDA 患者的临床使用，并且被证明是有效和安全的，与其他铁制剂相比，治疗指数更好。类似的增加铁吸收的性质也被 8-羟基喹啉、tropolone、2-羟基-4-甲氧基吡啶-1-氧化物及其相关类似物的亲脂性铁复合物所证明。KHP 铁复合物与天然螯合剂、药物、金属离子、蛋白质和其他分子的相互作用似乎会影响铁和 KHP 螯合剂的药理和代谢作用。从麦芽酚、KHP 和类似的亲脂性螯合剂的引入，可以预见 IDA 治疗和其他可能的临床应用的新时代，例如治疗诊断和抗癌制剂以及金属放射性示踪剂在诊断医学中的应用。
