Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology
Abstract
:1. Introduction
2. Pharmacological and Toxicological Considerations in the Use of Deferiprone against COVID-19
2.1. Pharmacological Properties and Effects of Deferiprone
2.2. Toxicological Aspects of Deferiprone Therapy
3. Deferiprone Targeting Molecules and Metabolic Pathways of COVID-19
3.1. Iron Chelation and Antioxidant Effects of Deferiprone in Relation to COVID-19
3.2. Targeting of Oxidative Stress Toxicity, Ferroptosis and Increase in Serum Ferritin Production by Deferiprone
3.3. Targeting Hypoxia in COVID-19 by Deferiprone
3.4. The Antiviral Effects of Deferiprone
3.5. The Prospects for the Use of Deferiprone against Microbial Infections and Sepsis in COVID-19
4. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Chemical and physicochemical properties |
---|
Molecular weight: 139. Molecular weight of iron complex: 470. |
Charge of L1 and iron complex at pH 7.4: neutral. |
Partition coefficient (n-octanol/water): 0.19 (hydrophilic). |
Stability constant (Log β) of deferiprone iron complex: 35. |
Clinical and biological effects |
Recommended dose in different categories of patients including combination with other chelating drugs: 10–100 mg/kg/day. |
Effect of deferiprone on iron absorption: decrease of iron absorption. |
Iron removal from diferric transferrin in iron loaded patients: removal of about 40% of iron at deferiprone concentrations of greater than 0.1 mM. Iron removal from ferritin and hemosiderin. |
Differential iron removal from various organs of iron loaded patients: preferential iron removal of excess iron from the heart but also from liver, spleen and pancreas of iron loaded patients. Efficacy in iron removal is related to dose. |
Iron redistribution in diseases of iron metabolism: Deferiprone can cause iron redistribution from iron deposits and also through transferrin from the reticuloendothelial system to the erythron in the anemia of chronic disease. Similar effects of excess iron redistribution is observed in patients with neurodegenerative diseases |
Increase excretion of metals other than iron, e.g., zinc (Zn) and aluminum (Al): increased Zn excretion in iron loaded patients, following long-term treatments. Increase Al excretion in renal dialysis patients. |
Iron mobilization and excretion of chelator metabolite iron complexes: no iron binding and no increase in iron excretion by the deferiprone glucuronide metabolite. |
Combination chelation therapy: Combination therapies of all chelating drugs are more effective in iron excretion than monotherapies. The International Committee On Chelation of deferiprone and deferoxamine combination protocol causes normalization of the iron stores in thalassemia patients. |
Metabolism and pharmacokinetics |
Metabolite(s): The deferiprone−gluguronite conjugate is cleared through the urine but have no iron chelation properties. |
T1/2 absorption of deferiprone: 0.7–32 min. T max of deferiprone: mostly within 1 h on empty stomach. |
T1/2 elimination of deferiprone: 47–134 min at 35–71 mg/kg dose. |
T1/2 elimination of the deferiprone iron complex: estimated within 47–134 min. |
T max of the L1 iron complex: estimated within 1 h. T max of the metabolite deferiprone-glucuronide: 1–3 h. |
Route of elimination of deferiprone and its iron complex: urine. |
Categories of patients with iron overload |
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Beta-thalassemia major |
Beta-thalassemia intermedia |
HbE β-thalassemia |
HbS β-thalassemia |
Sickle cell anemia |
Myelodysplastic syndrome |
Aplastic anemia |
Fanconi’s anemia |
Blackfan-Diamond anemia |
Pyruvate kinase deficiency |
Idiopathic hemochromatosis |
Iron overload in hemodialysis |
Juvenile hemochromatosis |
Categories of patients with normal iron stores |
Renal dialysis |
Rheumatoid arthritis |
Malaria |
HIV |
Breast cancer |
Prostate cancer |
Parkinson’s disease |
Alzheimer’s disease |
Friedreich’s Ataxia |
Neurodegeneration with brain iron accumulation |
Pantothenate kinase 2-associated neurodegeneration (PKAN) |
Glomerulonephritis and diabetic nephropathy |
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Kontoghiorghes, G.J. Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology. Int. J. Mol. Sci. 2022, 23, 6735. https://doi.org/10.3390/ijms23126735
Kontoghiorghes GJ. Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology. International Journal of Molecular Sciences. 2022; 23(12):6735. https://doi.org/10.3390/ijms23126735
Chicago/Turabian StyleKontoghiorghes, George J. 2022. "Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology" International Journal of Molecular Sciences 23, no. 12: 6735. https://doi.org/10.3390/ijms23126735