{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:10:14Z","timestamp":1789013414919,"version":"build-2803163510"},"reference-count":220,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The trimaltol iron complex (International Non-proprietary Name: ferric maltol) was originally designed, synthesised, and screened in vitro and in vivo in 1980\u20131981 by Kontoghiorghes G.J. following his discovery of the novel alpha-ketohydroxyheteroaromatic (KHP) class of iron chelators (1978\u20131981), 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms22115546","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T12:38:01Z","timestamp":1621859881000},"page":"5546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-7340","authenticated-orcid":false,"given":"George","family":"Kontoghiorghes","sequence":"first","affiliation":[{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annita","family":"Kolnagou","sequence":"additional","affiliation":[{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Demetriou","sequence":"additional","affiliation":[{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Neocleous","sequence":"additional","affiliation":[{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kontoghiorghe","sequence":"additional","affiliation":[{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100866","DOI":"10.1016\/j.mam.2020.100866","article-title":"Basics and principles of cellular and systemic iron homeostasis","volume":"75","author":"Katsarou","year":"2020","journal-title":"Mol. 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