Synthesis of Deferiprone as a Widely Used Iron-Chelating Drug for the Treatment of Iron-Overload Diseases

Document Type : Original Article

Authors

1 Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Medicinal Chemistry, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Thalassemia is a genetic disease that significantly affects human health. The common treatment of thalassemia is the regular injection of red blood cell, which is associated with the accumulation of iron in different tissues of the body, and makes chelation therapy necessary. Deferiprone and deferoxamine are broadly used as iron chelating agents in the vast majority of thalassemia cases. In this study, an efficient method for the synthesis of deferiprone was used by reacting maltol with methylamine in a mixture of water and ethanol as solvent. The structure of deferiprone was assigned using different spectroscopic techniques such as IR, 1H-NMR, and 13C-NMR. The advantages of this pathway are simple, practical, one-pot cascade, mild condition and high yield. The statistics of the Ministry of Health of Iran show the growing trend of deferiprone drug consumption in the country. Therefore, the domestic preparation of this drug can help the pharmaceutical industry in order to reduce costs and make it available for target patients.
Keywords: Synthesis, Deferiprone, Maltol, Methylamine, Iron chelating agent.

Highlights

Razieh Sabet (Google Scholar)

Keywords

References

1.    Kontoghiorghes GJ, Kleanthous M, Kontoghiorghe CN. The History of Deferiprone (L1) and the Paradigm of the Complete Treatment of Iron Overload in Thalassaemia. Mediterr J Hematol Infect Dis. 2020 Jan 1;12(1):e2020011. doi: 10.4084/MJHID.2020.011. PMID: 31934321; PMCID: PMC6951358.
2.    Binding A, Ward R, Tomlinson G, Kuo KHM. Deferiprone exerts a dose-dependent reduction of liver iron in adults with iron overload. Eur J Haematol. 2019 Aug;103(2):80-87. doi: 10.1111/ejh.13244. Epub 2019 May 30. PMID: 31066943.
3.    Hider RC, Hoffbrand AV. The Role of Deferiprone in Iron Chelation. N Engl J Med. 2018 Nov 29;379(22):2140-2150. doi: 10.1056/NEJMra1800219. PMID: 30485781.
4.    Klopstock T, Tricta F, Neumayr L, Karin I, Zorzi G, Fradette C, et al. Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study. Lancet Neurol. 2019 Jul;18(7):631-642. doi: 10.1016/S1474-4422(19)30142-5. PMID: 31202468.
5.    Timoshnikov VA, Kobzeva TV, Polyakov NE, Kontoghiorghes GJ. Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone. Int J Mol Sci. 2020 May 31;21(11):3967. doi: 10.3390/ijms21113967. PMID: 32486511; PMCID: PMC7312906.
6.    Elalfy MS, Hamdy M, El-Beshlawy A, Ebeid FSE, Badr M, Kanter J, et al. Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years. Blood Adv. 2023 Feb 28;7(4):611-619. doi: 10.1182/bloodadvances.2021006778. PMID: 36018224; PMCID: PMC9979751.
7.    Kontoghiorghes GJ. Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology. Int J Mol Sci. 2022 Jun 16;23(12):6735. doi: 10.3390/ijms23126735. PMID: 35743183; PMCID: PMC9223898.
8.    Flores Martin A, Shanmugarajah P, Hoggard N, Hadjivassiliou M. Treatment Response of Deferiprone in Infratentorial Superficial Siderosis: a Systematic Review. Cerebellum. 2021 Jun;20(3):454-461. doi: 10.1007/s12311-020-01222-7. Epub 2021 Jan 6. PMID: 33409768; PMCID: PMC8213658.
9.    Fassihi A, Abedi D, Saghaie L, Sabet R, Fazeli H, Bostaki G, et al. Synthesis, antimicrobial evaluation and QSAR study of some 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives. Eur J Med Chem. 2009 May;44(5):2145-57. doi: 10.1016/j.ejmech.2008.10.022. Epub 2008 Oct 30. PMID: 19056147.
10.    Hassani B, Zare F, Emami L, Khoshneviszadeha M, Fazel R, Kave N, et al., Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities. RSC Adv. 2023 Sept; 13(46):32433-32443. doi: 10.1039/D3RA06490E.
11.    Sadeghian S, Zare F, Goshtasbi G, Fassihi A, Saghaie L, Zare P, et al., Synthesis, Antimicrobial Evaluation, Molecular Docking, and ADME Studies of Some Novel 3‐Hydroxypyridine‐4‐one Derivatives. ChemistrySelect. 2023 Nov 24;8(44):e202302408. doi: 10.1002/slct.202302408.
Trends in Pharmaceutical Sciences
Volume 10, Issue 1
March 2024
Pages 77-82

Files

Share

How to cite

Statistics