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Old Drugs for New Metal-Related Diseases
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Old Drugs for New Metal-Related Diseases

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 19177

Special Issue Editors

Dr. Joanna Izabela Lachowicz

E-Mail Website
Guest Editor
Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
Interests: medicinal chemistry and bioinorganic chemistry; analytical chemistry applied in medicine and biology
Prof. Dr. Mariusz Jaremko

E-Mail Website
Co-Guest Editor
King Abdullah University of Science and Technology
Interests: The research group of Professor Mariusz Jaremko is focused on understanding and describing the basic principles of protein folding and misfolding, as well as the behavior of peptides and intrinsically disordered proteins (IDPs) under different conditions, including conditions as close as possible to the physiological ones. To achieve these scientific goals, state-of-the-art techniques of biomolecular NMR spectroscopy, together with other biophysical tools, are used. Understanding the biological phenomena which rule protein folding and dynamics would allow for the design of new safe and biodegradable materials with desired physicochemical properties, as well as the rational design of new drugs and efficient therapies against numerous neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, and other protein aggregation-related diseases, like diabetes type II.
Dr. Pierpaolo Coni

E-Mail Website
Co-Guest Editor
University of Cagliari
Interests: molecular biology related to the cancer and neurodegeneration processes

Special Issue Information

Dear Colleagues,

Among all known metal ions, several are essential for human life. Others are toxic for humans, even if they are used in medicine. Although the biochemistry of metal ions dates to the previous century, it remains an open field for research projects. As an inseparable part of metal biochemistry, metal ion chelators accompany metal ions as they leave (when in excess) or enter the body (when insufficient). Metal complexes can be used for diagnostics in vitro and in vivo, for metal biopathway studies, or even to kill pathological cells. Different genetic diseases are caused by metal excess or insufficiency: for example, in beta-thalassemia, Wilson’s and Menkes’ diseases. In recent years, further pathologies have been related to metal ions, such as amyloid diseases, neurodegeneration and diabetes. Finally, metal pollution of the environment leads to metal intoxication of humans and animals.

The current costly and time-consuming paradigm of drug discovery is inefficient in combatting rapidly emerging metal-related diseases. Cost, time, and safety are the reasons to revisit existing drugs.

This Special Issue aims to bring together recent research and experience on metal–drug coordination studies, innovative techniques in metal–drug investigations, and drug reposition studies for metal-related diseases. We invite researchers to contribute original research and review articles on recent advances and applications in this field of drug repositioning for metal-related diseases that is receiving so much attention in medicinal chemistry.

Dr. Joanna Izabela Lachowicz
Prof. Dr. Mariusz Jaremko
Dr. Pierpaolo Coni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Metal–drug interactions
  • Drug repositioning/redirecting
  • Metal related diseases
  • Metal toxicity
  • Bioinorganic chemistry
  • Medicinal chemistry
  • Chelation therapy

Published Papers (4 papers)

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Research

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19 pages, 5988 KiB  
Article
Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin
by Sherin Abdelrahman, Mawadda Alghrably, Marcello Campagna, Charlotte Armgard Emma Hauser, Mariusz Jaremko and Joanna Izabela Lachowicz
Molecules 2021, 26(16), 4730; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26164730 - 05 Aug 2021
Cited by 21 | Viewed by 3250
Abstract
Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk [...] Read more.
Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly, metformin-treated diabetic patients have lower cancer incidence. Here, we show that metformin forms stable complexes with copper (II) ions. Both copper(I)/metformin and copper(II)/metformin complexes form adducts with glutathione, the main intracellular antioxidative peptide, found at high levels in cancer cells. Metformin reduces cell number and viability in SW1222 and K562 cells, as well as in K562-200 multidrug-resistant cells. Notably, the antiproliferative effect of metformin is enhanced in the presence of copper ions. Full article
(This article belongs to the Special Issue Old Drugs for New Metal-Related Diseases)
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Review

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22 pages, 560 KiB  
Review
Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy
by Joanna Izabela Lachowicz, Luigi Isaia Lecca, Federico Meloni and Marcello Campagna
Molecules 2021, 26(21), 6639; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216639 - 02 Nov 2021
Cited by 7 | Viewed by 2191
Abstract
An increasing number of pathologies correlates with both toxic and essential metal ions dyshomeostasis. Next to known genetic disorders (e.g., Wilson’s Disease and β-Thalassemia) other pathological states such as neurodegeneration and diabetes are characterized by an imbalance of essential metal ions. Metal ions [...] Read more.
An increasing number of pathologies correlates with both toxic and essential metal ions dyshomeostasis. Next to known genetic disorders (e.g., Wilson’s Disease and β-Thalassemia) other pathological states such as neurodegeneration and diabetes are characterized by an imbalance of essential metal ions. Metal ions can enter the human body from the surrounding environment in the form of free metal ions or metal-nanoparticles, and successively translocate to different tissues, where they are accumulated and develop distinct pathologies. There are no characteristic symptoms of metal intoxication, and the exact diagnosis is still difficult. In this review, we present metal-related pathologies with the most common onsets, biomarkers of metal intoxication, and proper techniques of metal qualitative and quantitative analysis. We discuss the possible role of drugs with metal-chelating ability in metal dyshomeostasis, and present recent advances in therapies of metal-related diseases. Full article
(This article belongs to the Special Issue Old Drugs for New Metal-Related Diseases)
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19 pages, 797 KiB  
Review
Zinc as a Drug for Wilson’s Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury
by Pierpaolo Coni, Giuseppina Pichiri, Joanna Izabela Lachowicz, Alberto Ravarino, Francesca Ledda, Daniela Fanni, Clara Gerosa, Monica Piras, Ferdinando Coghe, Yukio Gibo, Flaviana Cau, Massimo Castagnola, Peter Van Eyken, Luca Saba, Marco Piludu and Gavino Faa
Molecules 2021, 26(21), 6614; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216614 - 31 Oct 2021
Cited by 12 | Viewed by 4420
Abstract
Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their [...] Read more.
Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson’s disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson’s disease. On the basis of the similarities, at histological level, between Wilson’s disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people. Full article
(This article belongs to the Special Issue Old Drugs for New Metal-Related Diseases)
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21 pages, 1924 KiB  
Review
Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator
by Denise Bellotti and Maurizio Remelli
Molecules 2021, 26(11), 3255; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26113255 - 28 May 2021
Cited by 48 | Viewed by 8651
Abstract
Deferoxamine B is an outstanding molecule which has been widely studied in the past decade for its ability to bind iron and many other metal ions. The versatility of this metal chelator makes it suitable for a number of medicinal and analytical applications, [...] Read more.
Deferoxamine B is an outstanding molecule which has been widely studied in the past decade for its ability to bind iron and many other metal ions. The versatility of this metal chelator makes it suitable for a number of medicinal and analytical applications, from the well-known iron chelation therapy to the most recent use in sensor devices. The three bidentate hydroxamic functional groups of deferoxamine B are the centerpiece of its metal binding ability, which allows the formation of stable complexes with many transition, lanthanoid and actinoid metal ions. In addition to the ferric ion, in fact, more than 20 different metal complexes of deferoxamine b have been characterized in terms of their chemical speciation in solution. In addition, the availability of a terminal amino group, most often not involved in complexation, opens the way to deferoxamine B modification and functionalization. This review aims to collect and summarize the available data concerning the complex-formation equilibria in solutions of deferoxamine B with different metal ions. A general overview of the progress of its applications over the past decade is also discussed, including the treatment of iron overload-associated diseases, its clinical use against cancer and neurodegenerative disorders and its role as a diagnostic tool. Full article
(This article belongs to the Special Issue Old Drugs for New Metal-Related Diseases)
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