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Inorganics
Special Issues
Tumor Inhibiting Metal Complexes
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Tumor Inhibiting Metal Complexes

A special issue of Inorganics (ISSN 2304-6740). This special issue belongs to the section "Bioinorganic Chemistry".

Deadline for manuscript submissions: closed (31 May 2017) | Viewed by 33380

Special Issue Editors

Prof. Dr. Wolfgang Weigand

E-Mail Website
Guest Editor
Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-Universität Jena, Humboldt Str. 8, 07743 Jena, Germany
Interests: coordination chemistry with sulfur, selenium, and tellurium ligands; [FeFe]-hydrogenase mimics; electrocatalytic and photocatalytic H2 evolution; metal-containing antiproliferative compounds; prebiotic chemistry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Luigi Messori

E-Mail Website
Guest Editor
Laboratory of Metals in Medicine (MetMed), Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, Italy
Interests: bioinorganic chemistry; metals in medicine; gold complexes; ruthenium complexes; platinum complexes; zinc and copper complexes; ovarian cancer; MS; model protein

Special Issue Information

Dear Colleagues,

When Michel Peyrone, in 1844, first reported on a new compound named cis-diammine dichlorido platinum(II) he could have never envisioned what an important substance he had created. It was not until the 1960s, through a serendipitous finding of Barnett Rosenberg, that the huge potential of this complex gradually became apparent. Since then, the story of the discovery of the first platinum-based chemotherapeutic has been told numerous times and thousands of researchers worldwide have dedicated their research efforts to elucidate the still intriguing chemical, biochemical and medicinal properties of Peyrone’s compound, now better known as Cisplatin. Platinum-biomolecule interactions in general, platinum-nucleic acid as well as platinum-protein interactions in particular, have received considerable attention over the last 50 years. Recently, apart from platinum containing drugs, other antitumor active metal complexes have been developed and are becoming increasingly relevant in this research area. Metal complexes containing, e.g., ruthenium, osmium, gold, copper, and even organometallic compounds turned out to be promising candidates in anticancer therapy.

The focus of this Special Issue is to highlight the more recent developments in the field of platinum and non-platinum compounds for anticancer therapy. This Special Issue should cover the synthetic strategies of new inorganic compounds, create bridges between chemistry and biology, and discuss the pharmacological and medicinal aspects on the ground of the underlying chemical features. The final goal is to find new active molecules for clinical application and to understand and optimizes the mechanisms of the existing ones.

Prof. Dr. Wolfgang Weigand
Prof. Dr. Luigi Messori
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. Inorganics 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 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 complexes
  • Synthesis and characterization of anticancer drugs
  • Health and medical applications
  • Pharmacological tests
  • Bioconjugates
  • Protein targeting
  • Bioanalytical methods
  • Cytotoxicity
  • Metal based drugs
  • Cisplatin platinum drugs
  • Ruthenium drug
  • Gold drugs
  • Osmium drugs
  • Copper drugs
  • Protein interactions
  • DNA interactions
  • Bioorganometallic chemistry
  • Bioinorganic chemistry

Published Papers (5 papers)

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Research

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2071 KiB  
Article
(18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity
by Goran N. Kaluđerović, Mirna Bulatović, Tamara Krajnović, Reinhard Paschke, Bojana B. Zmejkovski, Danijela Maksimović-Ivanić and Sanja Mijatović
Inorganics 2017, 5(3), 56; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics5030056 - 19 Aug 2017
Cited by 2 | Viewed by 4174
Abstract
Synthesis of platinum(II) conjugate with acetylated betulinic acid tris(hydroxymethyl)aminomethane ester (BATRIS) is presented (BATRISPt). HR-ESI-MS and multinuclear NMR spectroscopy, as well as elemental analysis were used for characterization of BATRISPt. Cytotoxicity (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), crystal violet (CV), and sulforhodamine B (SRB) assays) of [...] Read more.
Synthesis of platinum(II) conjugate with acetylated betulinic acid tris(hydroxymethyl)aminomethane ester (BATRIS) is presented (BATRISPt). HR-ESI-MS and multinuclear NMR spectroscopy, as well as elemental analysis were used for characterization of BATRISPt. Cytotoxicity (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), crystal violet (CV), and sulforhodamine B (SRB) assays) of BA, BATRIS, BATRISPt, and cisplatin were assessed on seven different tumor cell lines: melanoma B16, colon HCT116 and DLD-1, adenocarcinoma HeLa, breast MCF-7, and anaplastic thyroid tumor 8505C and SW1736; as well as normal MRC-5 fibroblasts. Furthermore, the effect of the mentioned compounds on the apoptosis (Annexin V/PI assay) and autophagy induction (acridine orange (AO) assay) as well as caspase 3, 8, and 9 activation were investigated on the selected B16 melanoma cell line. BATRISPt showed lower activity than BA, BATRIS, or cisplatin. All tested compounds triggered apoptosis in B16 cells. Induction of autophagy was observed in B16 cells exposed only to BATRIS. On the other hand, new conjugate activates caspases 8 and 9 in B16 cells with higher impact than BATRIS or cisplatin alone. Full article
(This article belongs to the Special Issue Tumor Inhibiting Metal Complexes)
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2095 KiB  
Article
Synthesis and In Vitro (Anticancer) Evaluation of η6-Arene Ruthenium Complexes Bearing Stannyl Ligands
by Olivier Renier, Connor Deacon-Price, Joannes E. B. Peters, Kunsulu Nurekeyeva, Catherine Russon, Simba Dyson, Siyabonga Ngubane, Judith Baumgartner, Paul J. Dyson, Tina Riedel, Haleden Chiririwa and Burgert Blom
Inorganics 2017, 5(3), 44; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics5030044 - 13 Jul 2017
Cited by 12 | Viewed by 6409
Abstract
Treatment of the known half-sandwich complexes of the type [(η6-C6H6)RuCl2(P(OR)3)] (R = Me or Ph) with SnCl2 yielded three new half-sandwich ruthenium complexes (C1–C3): [(η6-C6 [...] Read more.
Treatment of the known half-sandwich complexes of the type [(η6-C6H6)RuCl2(P(OR)3)] (R = Me or Ph) with SnCl2 yielded three new half-sandwich ruthenium complexes (C1–C3): [(η6-C6H6)RuCl(SnCl3)(P(OMe)3)] (C1), [(η6-C6H6)RuCl(SnCl3)(P(OPh)3)] (C2) and the bis-stannyl complex [(η6-C6H6)Ru(SnCl3)2(P(OMe)3)] (C3) by facile insertion of SnCl2 into the Ru–Cl bonds. Treatment of the known complexes [(η6-C6H6)RuCl(SnCl3)(PPh3)] and [(η6-C6H6)RuCl2(PPh3)] with 4-dimethylaminopyridine (DAMP) and ammonium tetrafluoroborate afforded the complex salts: [(η6-C6H6)Ru(SnCl3)(PPh3)(DAMP)]+BF4− (C4) and [(η6-C6H6)RuCl(PPh3)(DAMP)]+BF4− (C5) respectively. Complexes C1–C5 have been fully characterized by spectroscopic means (IR, UV–vis, multinuclear NMR, ESI–MS) and their thermal behaviour elucidated by thermal gravimetric analysis (TGA). Structural characterization by single crystal X-ray crystallography of the novel complex C2 and [(η6-C6H6)RuCl2(P(OPh)3)], the latter having escaped elucidation by this method, is also reported. Finally, the cytotoxicity of the complexes was determined on the A2780 (human ovarian cancer), A2780cisR (human ovarian cis-platin-resistant cancer), and the HEK293 (human embryonic kidney) cell lines and discussed, and an attempt is made to elucidate the effect of the stannyl ligand on cytotoxicity. Full article
(This article belongs to the Special Issue Tumor Inhibiting Metal Complexes)
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1537 KiB  
Article
A Cancer Stem Cell Potent Cobalt(III)–Cyclam Complex Bearing Two Tolfenamic Acid Moieties
by Paul B. Cressey, Arvin Eskandari and Kogularamanan Suntharalingam
Inorganics 2017, 5(1), 12; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics5010012 - 09 Feb 2017
Cited by 15 | Viewed by 6175
Abstract
Cancer stem cells (CSCs) are thought to be responsible for cancer relapse. CSCs are a subtype of cancer cells with the ability to differentiate, self-renew, and form secondary or tertiary tumors. Current cancer treatments—including chemotherapy, radiation, and surgery—effectively remove bulk cancer cells but [...] Read more.
Cancer stem cells (CSCs) are thought to be responsible for cancer relapse. CSCs are a subtype of cancer cells with the ability to differentiate, self-renew, and form secondary or tertiary tumors. Current cancer treatments—including chemotherapy, radiation, and surgery—effectively remove bulk cancer cells but are unable to eliminate CSCs. Here, we present the synthesis, characterization, and anti-CSC properties of a cobalt(III)–cyclam complex bearing two tolfenamic acid moieties, 3. Notably, 3 displays sub-micromolar potency towards breast CSCs and bulk breast cancer cells. Detailed mechanistic studies show that 3 is taken up readily by breast CSCs, enters the nucleus, causes DNA damage, and induces caspase-dependent apoptosis. Furthermore, 3 inhibits cyclooxygenase-2 (COX-2) expression in CSCs. The mechanism of action of 3 is similar to that of a naproxen-appended cobalt(III)–cyclam complex, 1 recently reported by our group. The advantage of 3 over 1 is that it has the potential to remove whole tumor populations (bulk cancer cells and CSCs) with a single dose. Full article
(This article belongs to the Special Issue Tumor Inhibiting Metal Complexes)
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8113 KiB  
Article
Steroid-Functionalized Titanocenes: Docking Studies with Estrogen Receptor Alpha
by Li Ming Gao, Wilson Maldonado, Xiomara Narváez-Pita, José A. Carmona-Negrón, Jesus Olivero-Verbel and Enrique Meléndez
Inorganics 2016, 4(4), 38; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics4040038 - 30 Nov 2016
Cited by 9 | Viewed by 4875
Abstract
Estrogen receptor alpha (ERα) is a transcription factor that is activated by hormones, with 17β-estradiol being its most active agonist endogenous ligand. ERα is also activated or inactivated by exogenous ligands. ER is overexpressed in hormone-dependent breast cancer, and one of the treatments [...] Read more.
Estrogen receptor alpha (ERα) is a transcription factor that is activated by hormones, with 17β-estradiol being its most active agonist endogenous ligand. ERα is also activated or inactivated by exogenous ligands. ER is overexpressed in hormone-dependent breast cancer, and one of the treatments for this type of cancer is the use of an ER antagonist to halt cell proliferation. We have previously reported four steroid-functionalized titanocenes: pregnenolone, dehydroepiandrosterone (DHEA), trans-androsterone, and androsterone. These steroids have hormonal activity as well as moderate antiproliferative activity, thus these steroids could act as vectors for the titanocene dichloride to target hormone-dependent cancers. Also, these steroids could increase the antiproliferative activity of the resulting titanocenes based on synergism. In order to elucidate which factors contribute to the enhanced antiproliferative activity of these steroid-functionalized titanocenes, we performed docking studies between ERα and the titanocenes and the steroids. The binding affinities and type of bonding interactions of the steroid-functionalized titanocenes with ERα are herein discussed. Full article
(This article belongs to the Special Issue Tumor Inhibiting Metal Complexes)
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Review

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4369 KiB  
Review
Anticancer Applications and Recent Investigations of Metallodrugs Based on Gallium, Tin and Titanium
by Younes Ellahioui, Sanjiv Prashar and Santiago Gómez-Ruiz
Inorganics 2017, 5(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics5010004 - 12 Jan 2017
Cited by 72 | Viewed by 10759
Abstract
For more than 100 years metal complexes have been extensively used in therapy and since the discovery of cisplatin the research in this field has expanded exponentially. The scientific community is always in search of new alternatives to platinum compounds and a wide [...] Read more.
For more than 100 years metal complexes have been extensively used in therapy and since the discovery of cisplatin the research in this field has expanded exponentially. The scientific community is always in search of new alternatives to platinum compounds and a wide variety of metallodrugs based on other metals have been reported with excellent therapeutic results. This short review focuses on the work that our research group has carried out since 2007 in collaboration with others and centers on the preparation of organogallium(III) compounds, organotin(IV) derivatives, and titanocene(IV) complexes together with the study of their cytotoxic anticancer properties. Full article
(This article belongs to the Special Issue Tumor Inhibiting Metal Complexes)
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