Special Issue "Metal-Based Drugs: Updates and Perspectives"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 30 September 2020.

Special Issue Editors

Prof. Dr. Daniela Montesarchio
Website
Guest Editor
Department of Chemical Sciences, University of Naples Federico II, via Cintia 4, 80126 Naples, Italy
Interests: Oligonucleotides; Nucleoside analogues; Unusual structures of DNA; G-quadruplex; Ru(III)-complexes; Pt(II)-complexes; Metal–DNA interactions; Small Molecule–DNA interactions
Special Issues and Collections in MDPI journals
Dr. Domenica Musumeci
Website
Guest Editor
Department of Chemical Sciences, University of Naples Federico II, via Cintia 4, 80126 Naples, Italy
Interests: Oligonucleotide analogues; PNA; Nucleopeptides; Peptidomimetics; Metal-based drugs; Ru(III)-complexes; Pt(II)-complexes; Metal–DNA interactions; Small Molecule–DNA interactions

Special Issue Information

Dear Colleagues,

The pharmaceutical potential of metals and their derivatives has been recognized for millennia in very different cultures, and with the advent of modern medicine, several metal-based drugs have been approved in clinic as effective therapeutic tools. Indeed, a large variety of metal compounds show significant bioactivity against a range of diseases, from the well-known anticancer activity of Pt(II)-complexes to the use of gold derivatives for the treatment of rheumatoid arthritis, just to name a few. Metal-based compounds can display an impressive chemical diversity, accompanied by a wide, easily and finely tunable reactivity, which allow their application as therapeutic and diagnostic tools in medicinal chemistry that is not readily accessible to the usual organic compounds.

This Special Issue of Pharmaceuticals on “Metal-Based Drugs: Updates and Perspectives” will include both regular articles and reviews focused on the most recent advances in the research into metals used in medicine, highlighting their pharmacological and diagnostic applications in several diseases. The major focus will be on the design, synthesis and optimization of novel complexes with higher efficacy and reduced toxic side effects compared to already existing metal-based drugs, on studies dealing with their mechanisms of action, the identification of their in vivo target, and approaches to validate their utility, along with their in vivo delivery, also taking advantage of specific or non-specific carriers (nanoparticles, liposomes, etc.).

With the aim of offering a dedicated forum open to all scientists engaged in this interdisciplinary research field, we particularly welcome contributions dealing with:

  • Metal-based complexes as therapeutic tools

Metallodrugs (design, synthesis, characterization, preclinical evaluation, pharmacokinetic studies, etc.) for the treatment of diseases, particularly with applications as:

anticancer, antimicrobial, antiparasitic, antibiotic, antiviral, anti-inflammatory, antiarthritic, antidiabetes, psychotropic, metallodrugs for the treatment of cardiovascular disorders, of metabolic diseases, of rare diseases, etc.

  • Metal-based complexes as diagnostic tools

Among others, diagnostic radiopharmaceuticals are powerful tools in the diagnosis of cancer, cardiological disorders, infections, kidney or liver abnormalities, neurological disorders, etc.

  • Studies of the mechanism of action of metallodrugs, with a special focus on the elucidation of their molecular targets
  • Studies on the biodistribution and fate of metallodrugs under in vivo conditions, including the physiological effects and toxicity issues.

Prof. Daniela Montesarchio
Dr. Domenica Musumeci
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 papers will be 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. Pharmaceuticals is an international peer-reviewed open access monthly 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 1000 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

  • metallodrugs
  • anticancer
  • antimicrobial
  • antiparasitic
  • antibiotic
  • antiviral
  • anti-inflammatory
  • antiarthritic
  • antidiabetes
  • psychotropic
  • cardiovascular disorders
  • metabolic diseases
  • rare diseases, etc.

Related Special Issues

Published Papers (7 papers)

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Research

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Open AccessArticle
The Impact of Iron Supplementation for Treating Anemia in Patients with Chronic Kidney Disease: Results from Pairwise and Network Meta-Analyses of Randomized Controlled Trials
Pharmaceuticals 2020, 13(5), 85; https://doi.org/10.3390/ph13050085 - 30 Apr 2020
Abstract
After relative erythropoietin deficiency, iron deficiency is the second most important contributing factor for anemia in chronic kidney disease (CKD) patients. Iron supplementation is a crucial part of the treatment of anemia in CKD patients, and intravenous (IV) iron supplementation is considered to [...] Read more.
After relative erythropoietin deficiency, iron deficiency is the second most important contributing factor for anemia in chronic kidney disease (CKD) patients. Iron supplementation is a crucial part of the treatment of anemia in CKD patients, and intravenous (IV) iron supplementation is considered to be superior to per os (PO) iron supplementation. The differences between the available formulations are poorly characterized. This report presents results from pairwise and network meta-analyses carried out after a comprehensive search in sources of published and unpublished studies, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations (International prospective register of systematic reviews PROSPERO reference ID: CRD42020148155). Meta-analytic calculations were performed for the outcome of non-response to iron supplementation (i.e., hemoglobin (Hgb) increase of <0.5–1.0 g/dL, or initiation/intensification of erythropoiesis-stimulating agent (ESA) therapy, or increase/change of iron supplement, or requirements of blood transfusion). A total of 34 randomized controlled trials (RCT) were identified, providing numerical data for analyses covering 93.7% (n = 10.097) of the total study population. At the network level, iron supplementation seems to have a more protective effect against the outcome of non-response before the start of dialysis than once dialysis is initiated, and some preparations seem to be more potent (e.g., ferumoxytol, ferric carboxymaltose), compared to the rest of iron supplements assessed (surface under the cumulative ranking area (SUCRA) > 0.8). This study provides parameters for adequately following-up patients requiring iron supplementation, by presenting the most performing preparations, and, indirectly, by making it possible to identify good responders among all patients treated with these medicines. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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Open AccessArticle
Peptide-Based Soft Hydrogels Modified with Gadolinium Complexes as MRI Contrast Agents
Pharmaceuticals 2020, 13(2), 19; https://doi.org/10.3390/ph13020019 - 21 Jan 2020
Abstract
Poly-aromatic peptide sequences are able to self-assemble into a variety of supramolecular aggregates such as fibers, hydrogels, and tree-like multi-branched nanostructures. Due to their biocompatible nature, these peptide nanostructures have been proposed for several applications in biology and nanomedicine (tissue engineering, drug delivery, [...] Read more.
Poly-aromatic peptide sequences are able to self-assemble into a variety of supramolecular aggregates such as fibers, hydrogels, and tree-like multi-branched nanostructures. Due to their biocompatible nature, these peptide nanostructures have been proposed for several applications in biology and nanomedicine (tissue engineering, drug delivery, bioimaging, and fabrication of biosensors). Here we report the synthesis, the structural characterization and the relaxometric behavior of two novel supramolecular diagnostic agents for magnetic resonance imaging (MRI) technique. These diagnostic agents are obtained for self-assembly of DTPA(Gd)-PEG8-(FY)3 or DOTA(Gd)-PEG8-(FY)3 peptide conjugates, in which the Gd-complexes are linked at the N-terminus of the PEG8-(FY)3 polymer peptide. This latter was previously found able to form self-supporting and stable soft hydrogels at a concentration of 1.0% wt. Analogously, also DTPA(Gd)-PEG8-(FY)3 and DOTA(Gd)-PEG8-(FY)3 exhibit the trend to gelificate at the same range of concentration. Moreover, the structural characterization points out that peptide (FY)3 moiety keeps its capability to arrange into β-sheet structures with an antiparallel orientation of the β-strands. The high relaxivity value of these nanostructures (~12 mM−1·s−1 at 20 MHz) and the very low in vitro cytotoxicity suggest their potential application as supramolecular diagnostic agents for MRI. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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Open AccessFeature PaperArticle
Role of the Metal Center in the Modulation of the Aggregation Process of Amyloid Model Systems by Square Planar Complexes Bearing 2-(2′-pyridyl)benzimidazole Ligands
Pharmaceuticals 2019, 12(4), 154; https://doi.org/10.3390/ph12040154 - 12 Oct 2019
Cited by 1
Abstract
The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2′-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aβ and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the [...] Read more.
The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2′-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aβ and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the interactions of the compounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. The results indicate that the compounds modulate the aggregation of the investigated peptides using different mechanisms, suggesting that the reactivity of the metal center and the physicochemical properties of the metals (rather than those of the ligands and the geometry of the metal compounds) play a crucial role in determining the anti-aggregation properties. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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Open AccessArticle
Colloidal Silver Induces Cytoskeleton Reorganization and E-Cadherin Recruitment at Cell-Cell Contacts in HaCaT Cells
Pharmaceuticals 2019, 12(2), 72; https://doi.org/10.3390/ph12020072 - 15 May 2019
Cited by 5
Abstract
Up until the first half of the 20th century, silver found significant employment in medical applications, particularly in the healing of open wounds, thanks to its antibacterial and antifungal properties. Wound repair is a complex and dynamic biological process regulated by several pathways [...] Read more.
Up until the first half of the 20th century, silver found significant employment in medical applications, particularly in the healing of open wounds, thanks to its antibacterial and antifungal properties. Wound repair is a complex and dynamic biological process regulated by several pathways that cooperate to restore tissue integrity and homeostasis. To facilitate healing, injuries need to be promptly treated. Recently, the interest in alternatives to antibiotics has been raised given the widespread phenomenon of antibiotic resistance. Among these alternatives, the use of silver appears to be a valid option, so a resurgence in its use has been recently observed. In particular, in contrast to ionic silver, colloidal silver, a suspension of metallic silver particles, shows antibacterial activity displaying less or no toxicity. However, the human health risks associated with exposure to silver nanoparticles (NP) appear to be conflicted, and some studies have suggested that it could be toxic in different cellular contexts. These potentially harmful effects of silver NP depend on various parameters including NP size, which commonly range from 1 to 100 nm. In this study, we analyzed the effect of a colloidal silver preparation composed of very small and homogeneous nanoparticles of 0.62 nm size, smaller than those previously tested. We found no adverse effect on the cell proliferation of HaCaT cells, even at high NP concentration. Time-lapse microscopy and indirect immunofluorescence experiments demonstrated that this preparation of colloidal silver strongly increased cell migration, re-modeled the cytoskeleton, and caused recruitment of E-cadherin at cell-cell junctions of human cultured keratinocytes. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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Review

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Open AccessReview
Biological Applications of Thiocarbohydrazones and Their Metal Complexes: A Perspective Review
Pharmaceuticals 2020, 13(1), 4; https://doi.org/10.3390/ph13010004 - 25 Dec 2019
Abstract
Although organic compounds account for more than 99% of currently approved clinical drugs, the established clinical use of cisplatin in cancer or auranofin in rheumatoid arthritis have paved the way to several research initiatives to identify metal-based drugs for a wide range of [...] Read more.
Although organic compounds account for more than 99% of currently approved clinical drugs, the established clinical use of cisplatin in cancer or auranofin in rheumatoid arthritis have paved the way to several research initiatives to identify metal-based drugs for a wide range of human diseases. Nitrogen and sulfur donor ligands, characterized by different binding motifs, have been the subject in recent years of one of the main research areas in coordination chemistry. Among the nitrogen/sulfur compounds, very little is known about thiocarbohydrazones (TCH), the higher homologues of the well-known thiosemicarbazones (TSC), and their metal complexes. The extra hydrazine moiety provides the ligands of variable metal binding modes, structural diversity and promising biological implications. The interesting coordination chemistry of TCH has mainly been focused on symmetric derivatives, which are relatively simple to synthesize while few examples of asymmetric ligands have been reported. This informative review on TCHs and their metal complexes will be helpful for improving the design of metal-based pharmaceuticals for applications ranging from anticancer to antinfective therapy. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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Open AccessReview
Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity
Pharmaceuticals 2019, 12(4), 146; https://doi.org/10.3390/ph12040146 - 26 Sep 2019
Cited by 2
Abstract
The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus [...] Read more.
The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low molecular weight Ru(III)-based compounds, some research groups have proposed the development of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III) complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at a molecular level, highlighting their pharmacological potential in tumour disease models and value for biomedical applications. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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Open AccessReview
Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver
Pharmaceuticals 2019, 12(3), 137; https://doi.org/10.3390/ph12030137 - 16 Sep 2019
Abstract
This article reviews the use of metal complexes as contrast agents (CA) and radiopharmaceuticals for the anatomical and functional imaging of the liver. The main focus was on two established imaging modalities: magnetic resonance imaging (MRI) and nuclear medicine, the latter including scintigraphy [...] Read more.
This article reviews the use of metal complexes as contrast agents (CA) and radiopharmaceuticals for the anatomical and functional imaging of the liver. The main focus was on two established imaging modalities: magnetic resonance imaging (MRI) and nuclear medicine, the latter including scintigraphy and positron emission tomography (PET). The review provides an overview on approved pharmaceuticals like Gd-based CA and 99mTc-based radiometal complexes, and also on novel agents such as 68Ga-based PET tracers. Metal complexes are presented by their imaging modality, with subsections focusing on their structure and mode of action. Uptake mechanisms, metabolism, and specificity are presented, in context with advantages and limitations of the diagnostic application and taking into account the respective imaging technique. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.


 

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