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Unconventional Anticancer Metallodrugs and Strategies to Improve their Pharmacological Profile

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ISBN: 9783039213153 9783039213160 Year: Pages: 204 DOI: 10.3390/books978-3-03921-316-0 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2019-12-09 11:49:15
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For the past 40 years, metal-based drugs have been widely used for the treatment of cancer. Cisplatin and follow-up drugs carboplatin (ParaplatinTM) and oxaliplatin (EloxatinTM) have been the gold standard for metallodrugs in clinical settings as antineoplastic agents. While effective, these drugs (either alone or in combination therapy) have faced a number of clinical challenges resulting from their limited spectrum of activity, high toxicity leading to significant side effects, resistance, poor water solubility, low bioavailability and short circulating time. In the past 10 years, various unconventional non-platinum metal-based agents have emerged as a potential alternative for cancer treatment. These compounds are highly effective and selective in cancers resistant to cisplatin and other chemotherapeutic agents. Research in this area has recently exploded with a relevant number of patents and clinical trials, in addition to reports in scientific journals. Furthermore, in parallel to the synthesis of coordination and organometallic compounds comprising many different metals and unconventional platinum-based derivatives, researchers are focused on optimizing mechanistic and pharmacological features of promising drug candidates. This Special Issue aims to highlight the latest advances in anticancer metallodrugs with a focus on unconventional anticancer agents, as well as novel activation, targeting and delivery strategies aimed at improving their pharmacological profile.

Iron as Therapeutic Targets in Human Diseases Volume 1

Authors: --- ---
ISBN: 9783039280827 9783039280834 Year: Pages: 472 DOI: 10.3390/books978-3-03928-083-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2020-04-07 23:07:08
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Abstract

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

Keywords

cinnamic acid derivatives --- soybean seed ferritin --- iron release --- binding ability --- Fe2+-chelating activity --- reducibility --- adverse event profile --- anaemia --- bioengineering --- labile iron --- intravenous iron --- iron-carbohydrate complex --- iron processing --- iron metabolism --- infection --- innate immunity --- hepcidin --- ferritin --- anemia of inflammation --- pharmaceutical targets --- iron deficiency anemia --- nutrient iron --- oral iron therapy --- FeSO4 --- NaFeEDTA --- non-transferrin-bound iron (NTBI) --- developing countries --- Indonesia --- neurodegeneration --- mitochondria --- therapy --- heme --- haem --- Iron-sulfur --- Friedreich Ataxia --- Oxidative stress --- Iron chelators --- iron deficiency --- anemia --- cancer --- hepcidin --- patient blood management --- malaria --- iron deficiency --- hepcidin --- TNF --- children --- Africa --- Anemia --- iron deficiency --- oral iron salts --- intravenous iron --- Sucrosomial® iron --- M cells --- bioavailability --- tolerability --- efficacy --- iron --- gut microbiota --- iron supplementation --- iron transporters --- mucosal immunity --- SCFA --- intestinal inflammation --- inflammatory bowel disease (IBD) --- colorectal cancer --- oxidative stress --- anaemia --- cardiovascular disease --- chronic kidney disease --- IV iron therapy --- bone homeostasis --- iron overload --- iron deficiency --- osteoclast --- osteoblast --- osteoporosis --- neurodegeneration with brain iron accumulation --- iron chelation therapy --- multifunctional iron chelators --- fluorescent iron chelator --- 3-hydroxy-4-pyridinone --- fluorophore --- rhodamine --- membrane interactions --- bacteria --- antibacterial activity --- histidine --- iron --- anemia --- oxidative stress --- kidney --- chelation --- iron --- retina --- age-related macular degeneration (AMD) --- iron --- lipid --- obesity --- cancer --- neurodegeneration --- iron chelation --- phlebotomy --- NCOA4 --- ferritinophagy --- iron homeostasis --- erythropoiesis --- ferroptosis --- cancer --- Tfr2 --- iron metabolism --- hepcidin --- erythropoiesis --- SNC --- ferritin --- iron mobilization --- chaotropes --- flavin nucleotide --- electron transfer --- kinetics --- ferritin --- iron --- iron delivery --- nanotechnology --- nanocage --- drug delivery --- inflammation --- serum biomarker --- iron metabolism --- hepcidin --- ferroportin --- hemochromatosis --- anemia --- hepcidin --- iron deficiency anemia --- iron dextran --- neonatal period --- pig --- supplementation --- Alzheimer’s disease --- neuroinflammation --- neurodegeneration --- cytokines --- neuroimmune responses --- iron --- genetic hemochromatosis --- non transferrin bound iron --- hepcidin --- ferroportin --- venesections --- Anemia of chronic disease --- anemia of inflammation --- hepcidin --- anti-hepcidin therapy --- iron supplementation --- macrophage --- central nurse macrophage --- red pulp macrophage --- Kupffer cell --- iron metabolism --- erythropoiesis --- erythroblastic islands --- erythrophagocytosis --- inflammation --- iron homeostasis --- lung diseases --- oxygen sensing --- hypoxia --- ferritin --- hereditary hyperferritinemia --- hereditary hypoferritinemia --- iron metabolism --- cataracts syndrome --- neurodegenerative disease --- n/a --- iron --- neurodegeneration --- NBIA --- hepcidin --- iron --- lung --- acute lung injury --- COPD --- lung infection --- cystic fibrosis --- iron --- anaemia --- infection --- malaria --- immunity --- brain development --- growth --- microbiome --- hepcidin --- ferritin --- iron supplementation --- infants --- children --- low and middle income countries --- liver --- iron --- hepcidin --- Mek/Erk --- Hfe --- Bmp/Smad --- iron --- mycobacteria --- immunity --- Alzheimer’s disease --- iron homeostasis --- ferroptosis --- senescence --- chelators --- macrophages --- iron --- metabolism --- inflammation --- iron --- ferritin --- acute kidney injury --- chronic kidney disease --- vascular calcification --- iron --- hepcidin --- ferroportin --- Interleukin-6 --- infection --- rheumatoid arthritis --- iron homeostasis --- iron absorption --- non-haem iron --- flavonoids --- developmental --- iron deficiency anemia --- neonatal --- transferrin receptor --- treatment --- hemochromatosis --- HFE --- natural history --- T lymphocytes --- MHC --- CD8+ T cells --- prevention --- iron homeostasis --- hepcidin --- protein binding --- peritoneal dialysis --- iron --- hepcidin --- iron regulatory proteins --- cardiomyocyte --- chronic heart failure --- pulmonary arterial smooth muscle cells --- pulmonary arterial hypertension --- iron --- brain --- neurophysiology --- cognition --- social behavior --- didox --- iron chelators --- antitumor compound --- iron metabolism --- RRM2 --- SLC40A1 --- ferroportin --- iron overload --- non-HFE --- ferritin --- hemochromatosis --- iron --- chelation --- neurodegenerative diseases --- pituitary --- brain --- hemopexin --- heme homeostasis --- iron homeostasis --- hemolysis --- haptoglobin --- ferroptosis --- inflammation --- biomarker --- heme oxygenase --- liver --- microbiome --- trauma --- hemorrhage --- iron metabolism --- hepcidin --- iron homeostasis --- ferroportin --- n/a

Iron as Therapeutic Targets in Human Diseases Volume 2

Authors: --- ---
ISBN: 9783039281145 9783039281152 Year: Pages: 440 DOI: 10.3390/books978-3-03928-115-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2020-04-07 23:07:08
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Abstract

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

Keywords

cinnamic acid derivatives --- soybean seed ferritin --- iron release --- binding ability --- Fe2+-chelating activity --- reducibility --- adverse event profile --- anaemia --- bioengineering --- labile iron --- intravenous iron --- iron-carbohydrate complex --- iron processing --- iron metabolism --- infection --- innate immunity --- hepcidin --- ferritin --- anemia of inflammation --- pharmaceutical targets --- iron deficiency anemia --- nutrient iron --- oral iron therapy --- FeSO4 --- NaFeEDTA --- non-transferrin-bound iron (NTBI) --- developing countries --- Indonesia --- neurodegeneration --- mitochondria --- therapy --- heme --- haem --- Iron-sulfur --- Friedreich Ataxia --- Oxidative stress --- Iron chelators --- iron deficiency --- anemia --- cancer --- hepcidin --- patient blood management --- malaria --- iron deficiency --- hepcidin --- TNF --- children --- Africa --- Anemia --- iron deficiency --- oral iron salts --- intravenous iron --- Sucrosomial® iron --- M cells --- bioavailability --- tolerability --- efficacy --- iron --- gut microbiota --- iron supplementation --- iron transporters --- mucosal immunity --- SCFA --- intestinal inflammation --- inflammatory bowel disease (IBD) --- colorectal cancer --- oxidative stress --- anaemia --- cardiovascular disease --- chronic kidney disease --- IV iron therapy --- bone homeostasis --- iron overload --- iron deficiency --- osteoclast --- osteoblast --- osteoporosis --- neurodegeneration with brain iron accumulation --- iron chelation therapy --- multifunctional iron chelators --- fluorescent iron chelator --- 3-hydroxy-4-pyridinone --- fluorophore --- rhodamine --- membrane interactions --- bacteria --- antibacterial activity --- histidine --- iron --- anemia --- oxidative stress --- kidney --- chelation --- iron --- retina --- age-related macular degeneration (AMD) --- iron --- lipid --- obesity --- cancer --- neurodegeneration --- iron chelation --- phlebotomy --- NCOA4 --- ferritinophagy --- iron homeostasis --- erythropoiesis --- ferroptosis --- cancer --- Tfr2 --- iron metabolism --- hepcidin --- erythropoiesis --- SNC --- ferritin --- iron mobilization --- chaotropes --- flavin nucleotide --- electron transfer --- kinetics --- ferritin --- iron --- iron delivery --- nanotechnology --- nanocage --- drug delivery --- inflammation --- serum biomarker --- iron metabolism --- hepcidin --- ferroportin --- hemochromatosis --- anemia --- hepcidin --- iron deficiency anemia --- iron dextran --- neonatal period --- pig --- supplementation --- Alzheimer’s disease --- neuroinflammation --- neurodegeneration --- cytokines --- neuroimmune responses --- iron --- genetic hemochromatosis --- non transferrin bound iron --- hepcidin --- ferroportin --- venesections --- Anemia of chronic disease --- anemia of inflammation --- hepcidin --- anti-hepcidin therapy --- iron supplementation --- macrophage --- central nurse macrophage --- red pulp macrophage --- Kupffer cell --- iron metabolism --- erythropoiesis --- erythroblastic islands --- erythrophagocytosis --- inflammation --- iron homeostasis --- lung diseases --- oxygen sensing --- hypoxia --- ferritin --- hereditary hyperferritinemia --- hereditary hypoferritinemia --- iron metabolism --- cataracts syndrome --- neurodegenerative disease --- n/a --- iron --- neurodegeneration --- NBIA --- hepcidin --- iron --- lung --- acute lung injury --- COPD --- lung infection --- cystic fibrosis --- iron --- anaemia --- infection --- malaria --- immunity --- brain development --- growth --- microbiome --- hepcidin --- ferritin --- iron supplementation --- infants --- children --- low and middle income countries --- liver --- iron --- hepcidin --- Mek/Erk --- Hfe --- Bmp/Smad --- iron --- mycobacteria --- immunity --- Alzheimer’s disease --- iron homeostasis --- ferroptosis --- senescence --- chelators --- macrophages --- iron --- metabolism --- inflammation --- iron --- ferritin --- acute kidney injury --- chronic kidney disease --- vascular calcification --- iron --- hepcidin --- ferroportin --- Interleukin-6 --- infection --- rheumatoid arthritis --- iron homeostasis --- iron absorption --- non-haem iron --- flavonoids --- developmental --- iron deficiency anemia --- neonatal --- transferrin receptor --- treatment --- hemochromatosis --- HFE --- natural history --- T lymphocytes --- MHC --- CD8+ T cells --- prevention --- iron homeostasis --- hepcidin --- protein binding --- peritoneal dialysis --- iron --- hepcidin --- iron regulatory proteins --- cardiomyocyte --- chronic heart failure --- pulmonary arterial smooth muscle cells --- pulmonary arterial hypertension --- iron --- brain --- neurophysiology --- cognition --- social behavior --- didox --- iron chelators --- antitumor compound --- iron metabolism --- RRM2 --- SLC40A1 --- ferroportin --- iron overload --- non-HFE --- ferritin --- hemochromatosis --- iron --- chelation --- neurodegenerative diseases --- pituitary --- brain --- hemopexin --- heme homeostasis --- iron homeostasis --- hemolysis --- haptoglobin --- ferroptosis --- inflammation --- biomarker --- heme oxygenase --- liver --- microbiome --- trauma --- hemorrhage --- iron metabolism --- hepcidin --- iron homeostasis --- ferroportin --- n/a

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