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Metal Ions in Life Sciences

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https://read.qxmd.com/read/30855115/chemical-and-clinical-aspects-of-metal-containing-antidotes-for-poisoning-by-cyanide
#1
Sigridur G Suman, Johanna M Gretarsdottir
Physiological metabolism of cyanide takes place by a single major pathway that forms non-toxic thiocyanate that is subsequently excreted. Rhodanese is the primary enzyme to execute metabolism of cyanide with minor pathways from other sulfurtransferases in vivo. The rhodanese enzyme depends on sulfur donor availability to metabolize cyanide and poisoning occurs at elevated cyanide concentrations in vivo. Cyanide interacts with over 40 metalloenzymes, but its lethal action is non-competitive inhibition of cytochrome c oxidase, halting cellular respiration and causing hypoxic anoxia...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855114/metal-compounds-in-the-development-of-antiparasitic-agents-rational-design-from-basic-chemistry-to-the-clinic
#2
Dinorah Gambino, Lucía Otero Á
Metal compounds seem to be a promising approach in the search of new therapeutic solutions for neglected tropical diseases. In this chapter, efforts in the design of prospective metal-based drugs for the treatment of Chagas disease, human African trypanosomiasis, and leishmaniasis are discussed. Careful selection of the metal center (including organometallic cores) and the types and number of coordinated ligands is essential for controlling the reactivity of the complexes and hence, tuning their biological properties...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855113/copper-depletion-as-a-therapeutic-strategy-in-cancer
#3
Jay Lopez, Divya Ramchandani, Linda Vahdat
Copper is an essential trace element that plays a critical role in a variety of basic biological functions, and serves as a key component in a number of copper-dependent enzymes that regulate such processes as cell proliferation, angiogenesis, and motility. A growing body of preclinical work has demonstrated that copper is essential to metastatic cancer progression, and may have a role in tumor growth, epithelial-mesenchymal transition, and the formation of the tumor microenvironment and pre-metastatic niche...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855112/cobalt-schiff-base-complexes-preclinical-research-and-potential-therapeutic-uses
#4
Elizabeth A Bajema, Kaleigh F Roberts, Thomas J Meade
The use of metals in medicine has grown impressively in recent years as a result of greatly advanced understanding of biologically active metal complexes and metal-containing proteins. One landmark in this area was the introduction of cisplatin and related derivatives as anticancer drugs. As the body of literature continues to expand, it is necessary to inspect sub-classes of this group with more acute detail. This chapter will review preclinical research of cobalt complexes coordinated by Schiff base ligands...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855111/manganese-its-role-in-disease-and-health
#5
Keith M Erikson, Michael Aschner
Manganese is an essential dietary element that functions primarily as a coenzyme in several biological processes. These processes include, but are not limited to, macronutrient metabolism, bone formation, free radical defense systems, and in the brain, ammonia clearance and neurotransmitter synthesis. It is a critical component in dozens of proteins and enzymes, and is found in all tissues. Concentrated levels of Mn are found in tissues rich in mitochondria and melanin, with both, liver, and pancreas having the highest concentrations under normal conditions...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855110/chromium-supplementation-in-human-health-metabolic-syndrome-and-diabetes
#6
Wolfgang Maret
After 40 years of significant work, it was generally accepted that chromium in its trivalent valence state, Cr(III), is an essential micronutrient for humans. This view began to be challenged around the turn of the millennium. Some investigators argue that its effects on glucose and lipid metabolism reflect a pharmacological rather than a nutritional mode of action while yet others express concern about the toxicity and safety of supplemental chromium. Understanding the conjectures requires a reflection on the different definitions of "essential" and a perspective on the development of the field, which in itself is a remarkable snippet of science history and education...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855109/developing-vanadium-as-an-antidiabetic-or-anticancer-drug-a-clinical-and-historical-perspective
#7
Debbie C Crans, LaRee Henry, Gabriel Cardiff, Barry I Posner
Vanadium has been known for centuries to have beneficial effects on health and has the potential to be used as an alternative to other diabetic and anticancer medicines. The beneficial effects of vanadium salts or organic compounds have been explored in vitro, ex vivo, and in vivo in animal and human studies. A consensus among researchers is that increased bioavailability of these compounds could markedly increase the efficacy of this class of compounds. In addition, because many commercially available vanadium derivatives are being used by body builders to enhance performance, more understanding of their mode of action is desirable...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855108/building-a-trojan-horse-siderophore-drug-conjugates-for-the-treatment-of-infectious-diseases
#8
Elzbieta Gumienna-Kontecka, Peggy L Carver
Antimicrobial resistance is a major global health problem, and novel approaches to solving this crisis are urgently required. The 'Trojan Horse' approach to solving this problem capitalizes on the innate need for iron by pathogens. Siderophores are low-molecular-weight iron chelators secreted extracellularly by pathogens to scavenge iron. Once bound to iron, the iron-siderophore complex returns to the pathogen to deliver its iron treasure. "Smuggling" antimicrobials into the pathogen is accomplished by linking them to siderophores for transport...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855107/iron-oxide-nanoparticle-formulations-for-supplementation
#9
Amy Barton Pai
Intravenous (IV) iron is widely used to provide supplementation when oral iron is ineffective or not tolerated. All commercially available intravenous iron formulations are comprised of iron oxyhydroxide cores coated with carbohydrates of varying structure and branch characteristics. The diameter of the iron-carbohydrate complexes ranges from 5-100 nm and meets criteria for nanoparticles. Clinical use of IV iron formulations entered clinical practice beginning of the late 1950s, which preceded the nanomedicine exploration frontier...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855106/infections-associated-with-iron-administration
#10
Manfred Nairz, Guenter Weiss
A dynamic interplay between the host and pathogen determines the course and outcome of infections. A central venue of this interplay is the struggle for iron, a micronutrient essential to both the mammalian host and virtually all microbes. The induction of the ironregulatory hormone hepcidin is an integral part of the acute phase response. Hepcidin switches off cellular iron export via ferroportin-1 and sequesters the metal mainly within macrophages, which limits the transfer of iron to the serum to restrict its availability for extracellular microbes...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855105/ironing-out-the-brain
#11
Roberta J Ward, Robert R Crichton
Our understanding of the broad principles of cellular and systemic iron homeostasis in man are well established with the exception of the brain. Most of the proteins involved in mammalian iron metabolism are present in the brain, although their distribution and precise roles in iron uptake, intracellular metabolism and export are still uncertain, as is the way in which systemic iron is transferred across the blood-brain barrier. We briefly review current concepts concerning the uptake and distribution of iron in the brain, before turning to the ways in which brain iron homeostasis might be regulated...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855104/iron-chelation-for-iron-overload-in-thalassemia
#12
Guido Crisponi, Valeria M Nurchi, Joanna I Lachowicz
This chapter is devoted to the chelation treatment of transfusion-dependent thalassemia patients. After a brief overview on the pathophysiology of iron overload and on the methods to quantify it in different organs, the chelation therapy is discussed, giving particular attention to the chemical and biomedical requisites. The main tasks of an iron chelator should be the scavenging of excess iron, allowing an equilibrium between iron supplied by transfusions and that removed with chelation, and protection of the individual from the poisonous effects of circulating iron...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855103/small-molecules-the-past-or-the-future-in-drug-innovation
#13
Anne Robert, Françoise Benoit-Vical, Yan Liu, Bernard Meunier
With the impressive development of molecular life sciences, one may have the feeling that biopharmaceuticals will dominate the world of drug design and production. This is partly due to the evolution of pharmaceutical industry, especially since the 1980s. As a matter of fact, small molecules are still dominating the field of drug innovation, in contradiction with claims predicting their downfall and the exponential raise of biopharmaceuticals. The strong association of chemistry with biochemistry and pharmacology has been the scientific base of the establishment and the success of strong powerful pharmaceutical companies throughout the twentieth century...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/30855102/metals-in-medicine-the-therapeutic-use-of-metal-ions-in-the-clinic
#14
Peggy L Carver
Metal ions are indispensable for living organisms. However, the roles of metal ions in humans is complex, and remains poorly understood. Imbalances in metal ion levels, due to genetic or environmental sources, are associated with a number of significant health issues. However, in clinical medicine, the role of metal ions and metal-based drugs is notable in three major areas: as metal-related diseases; as metal-based medicines (including drugs, imaging agents, and metal chelators); and as agents of metal-based toxicity...
January 14, 2019: Metal Ions in Life Sciences
https://read.qxmd.com/read/29394036/targeting-zinc-ii-signalling-to-prevent-cancer
#15
REVIEW
Silvia Ziliotto, Olivia Ogle, Kathryn M Taylor
Zinc is an important element that is gaining momentum as a potential target for cancer therapy. In recent years zinc has been accepted as a second messenger that is now recognized to be able to activate many signalling pathways within a few minutes of an extracellular stimulus by release of zinc(II) from intracellular stores. One of the major effects of this store release of zinc is to inhibit a multitude of tyrosine phosphatases which will prevent the inactivation of tyrosine kinases and hence, encourage further activation of tyrosine kinasedependent signalling pathways...
February 5, 2018: Metal Ions in Life Sciences
https://read.qxmd.com/read/29394035/copper-complexes-in-cancer-therapy
#16
REVIEW
Delphine Denoyer, Sharnel A S Clatworthy, Michael A Cater
Copper homeostasis is tightly regulated in both prokaryotic and eukaryotic cells to ensure sufficient amounts for cuproprotein biosynthesis, while limiting oxidative stress production and toxicity. Over the last century, copper complexes have been developed as antimicrobials and for treating diseases involving copper dyshomeostasis (e.g., Wilson's disease). There now exists a repertoire of copper complexes that can regulate bodily copper through a myriad of mechanisms. Furthermore, many copper complexes are now being appraised for a variety of therapeutic indications (e...
February 5, 2018: Metal Ions in Life Sciences
https://read.qxmd.com/read/29394034/iron-and-its-role-in-cancer-defense-a-double-edged-sword
#17
REVIEW
Frank Thévenod
Iron (Fe) is an essential metal, vital for biological functions, including electron transport, DNA synthesis, detoxification, and erythropoiesis that all contribute to metabolism, cell growth, and proliferation. Interactions between Fe and O2 can result in the generation of reactive oxygen species (ROS), which is based on the ability of Fe to redox cycle. Excess Fe may cause oxidative damage with ensuing cell death, but DNA damage may also lead to permanent mutations. Hence Fe is carcinogenic and may initiate tumor formation and growth, and also nurture the tumor microenvironment and metastasis...
February 5, 2018: Metal Ions in Life Sciences
https://read.qxmd.com/read/29394033/metallointercalators-and-metalloinsertors-structural-requirements-for-dna-recognition-and-anticancer-activity
#18
REVIEW
Ulrich Schatzschneider
As the carrier of the inheritable information in cells, DNA has been the target of metal complexes for over 40 years. In this chapter, the focus will be on non-covalent recognition of the highly structured DNA surface by substitutionally inert metal complexes capable of either sliding in between the normal base pairs as metallointercalators or flipping out thermodynamically destabilized mispaired nucleobases as metalloinsertors. While most of the compounds discussed are based on ruthenium(II) and rhodium(III) due to their stable octahedral coordination environment and low-spin 4d6 electronic configuration, most recent developments of alternative metal complexes, based on both transition metals and main group elements, will also be highlighted...
February 5, 2018: Metal Ions in Life Sciences
https://read.qxmd.com/read/29394032/antitumor-metallodrugs-that-target-proteins
#19
REVIEW
Matthew P Sullivan, Hannah U Holtkamp, Christian G Hartinger
Anticancer platinum-based drugs are widely used in the treatment of a variety of tumorigenic diseases. They have been identified to target DNA and thereby induce apoptosis in cancer cells. Their reactivity to biomolecules other than DNA has often been associated with side effects that many cancer patients experience during chemotherapy. The development of metal compounds that target proteins rather than DNA has the potential to overcome or at least reduce the disadvantages of commonly used chemotherapeutics...
February 5, 2018: Metal Ions in Life Sciences
https://read.qxmd.com/read/29394031/nucleic-acid-quadruplexes-and-metallo-drugs
#20
REVIEW
Ramon Vilar
Guanine-rich sequences of DNA can readily fold into tetra-stranded helical assemblies known as G-quadruplexes (G4s). It has been proposed that these structures play important biological roles in transcription, translation, replication, and telomere maintenance. Therefore, over the past 20 years they have been investigated as potential drug targets for small molecules including metal complexes. This chapter provides an overview of the different classes of metal complexes as G4-binders and discusses the application of these species as optical probes for G-quadruplexes as well as metallo-drugs...
February 5, 2018: Metal Ions in Life Sciences
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