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Inorganics
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Bioactivity of Transition Metal-Based Complexes
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Bioactivity of Transition Metal-Based Complexes

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

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 10602

Special Issue Editors

Dr. Snežana Jovanović-Stević

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Guest Editor
University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Svetozara Markovića 69, 34000 Kragujevac, Serbia
Interests: transition metal complexes; kinetics; biomolecules; interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Tanja Soldatović

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Guest Editor
Department of Natural-Mathematical Sciences, State University of Novi Pazar, 36300 Novi Pazar, Serbia
Interests: bioinorganic chemistry; medicinal inorganic chemistry; heterometallic complexes; biomolecules interactions; mechanism of antitumor activity
Special Issues, Collections and Topics in MDPI journals
Dr. Ralph Puchta

E-Mail Website
Guest Editor
Department of Chemistry and Pharmacy, Inorganic and organometallic chemistry, Egerlandstr. 1, 91058 Erlangen, Germany
Interests: theoretical oriented inorganic chemistry; beryllium; supramolecular chemistry; (bio)inorganic reaction mechanisms; super basic compounds "proton sponges"; enantiomerisation; aromaticity

Special Issue Information

Dear Colleagues,

The application of transition metal complexes in chemotherapy is well established. Cisplatin is the first cytostatic drug based on a metal ion used in the treatment of various types of cancers. However, serious side effects and drug resistance can occur during its clinical application. Thus, huge efforts are being made in the development of metal-based complexes in order to design the compound with a superior pharmacological response, as compared to cisplatin. In recent years, numerous complexes of platinum, palladium, ruthenium, gold, rhodium, osmium, iridium, zinc, copper, and other transition metals with significant antitumor activity against various carcinogenic cells in vitro and in vivo have been synthesized. In this Special Issue, we wish to address the most recent advances in the field of transition metal-based complexes and their potential clinical use by hosting a mix of original research articles and short critical reviews.

Dr. Snežana Jovanović-Stević
Dr. Tanja Soldatović
Dr. Ralph Puchta
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

  • transition metal complexes
  • biomolecules
  • interactions
  • biological activity

Published Papers (6 papers)

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Research

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16 pages, 2283 KiB  
Article
Enhancement of the Cytotoxicity of Quinazolinone Schiff Base Derivatives with Copper Coordination
by Ilona Gurgul, Jana Hricovíniová, Olga Mazuryk, Zuzana Hricovíniová and Małgorzata Brindell
Inorganics 2023, 11(10), 391; https://doi.org/10.3390/inorganics11100391 - 02 Oct 2023
Cited by 2 | Viewed by 1302
Abstract
Two copper(II) complexes (Cu-L1, Cu-L2) derived from 2,3-substituted quinazolinone Schiff base ligands (L1, L2) were prepared to examine their anticancer activity. Compounds were characterized using various spectroscopic methods (FTIR, NMR, UV-vis) and quantum-chemical calculations. The biological effects [...] Read more.
Two copper(II) complexes (Cu-L1, Cu-L2) derived from 2,3-substituted quinazolinone Schiff base ligands (L1, L2) were prepared to examine their anticancer activity. Compounds were characterized using various spectroscopic methods (FTIR, NMR, UV-vis) and quantum-chemical calculations. The biological effects of Cu(II) complexes bearing quinazolinone scaffolds were evaluated on two cancers’ cell lines (breast—MCF-7 and lung—A549), as well as on untransformed cells (keratinocytes—HaCaT). Copper complexes were highly cytotoxic, with IC50 in the low micromolar range, while the quinazoline ligands L1 and L2 remained inactive in inhibiting cell proliferation. Antioxidant activity was investigated in the model systems using DPPH and FRAP assays. The Cu-L1 and Cu-L2 complexes exhibited enhanced DPPH free radical scavenging efficiency compared to the L1 and L2 ligands, but their reducing ability was comparable to that of the free ligands. Evaluation of oxidative stress in vitro carried out by staining cells with various ROS-specific indicators showed reduced production of superoxide anion radical and hydrogen peroxide after treatment of cells with copper complexes. Such a negative impact on ROS formation in cells can lead to cellular redox imbalance and consequent cell death, among others, by inducing apoptosis and/or necrosis, depending on the copper complex used. We hypothesize that the high cytotoxic activity of the investigated copper complexes is apparently the result of multiple mechanisms of action, and the imbalance in the cellular antioxidant system partly contributes to the overall cytotoxic effect. Full article
(This article belongs to the Special Issue Bioactivity of Transition Metal-Based Complexes)
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21 pages, 3777 KiB  
Article
A Tridentate Cu(II) Complex with a 2-(4′-Aminophenyl)Benzothiazole Derivative: Crystal Structure and Biological Evaluation for Anticancer Activity
by Barbara Mavroidi, Marina Sagnou, Eleftherios Halevas, George Mitrikas, Fotis Kapiris, Penelope Bouziotis, Antonios G. Hatzidimitriou, Maria Pelecanou and Constantinos Methenitis
Inorganics 2023, 11(3), 132; https://doi.org/10.3390/inorganics11030132 - 20 Mar 2023
Viewed by 1250
Abstract
Herein, the synthesis, structural characterization and in vitro biological evaluation of a novel Cu(II) complex with the 2-(4-aminophenyl)benzothiazole pharmacophore conjugated with the (2-pyridinyl)methylamino chelating moiety is reported for the first time. A full characterization of the Cu(II) complex was conducted by X-ray crystallography, [...] Read more.
Herein, the synthesis, structural characterization and in vitro biological evaluation of a novel Cu(II) complex with the 2-(4-aminophenyl)benzothiazole pharmacophore conjugated with the (2-pyridinyl)methylamino chelating moiety is reported for the first time. A full characterization of the Cu(II) complex was conducted by X-ray crystallography, EPR, IR, elemental and MS analysis, and its binding to CT-DNA was investigated by UV-vis spectroscopy, ethidium bromide competition studies, circular dichroism, viscometry and thermal denaturation. The data clearly indicate that the Cu(II) complex interacts with CT-DNA via intercalation, registering a difference compared to previously reported Pt(II) and Pd(II) analogues. To evaluate the anticancer activity of the complex, a series of in vitro experiments against breast, glioblastoma, prostate and lung cancer cell lines along with healthy fibroblasts were implemented. Cytotoxicity, cellular uptake, intracellular ROS production, cell cycle and apoptosis analysis revealed an increased anticancer activity towards breast cancer cells that is accompanied by an induction in intracellular ROS levels and a significant G2/M arrest followed by apoptosis. Full article
(This article belongs to the Special Issue Bioactivity of Transition Metal-Based Complexes)
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13 pages, 2081 KiB  
Article
Half-Sandwich Nickelacarboranes Derived from [7-(MeO(CH2)2S)-7,8-C2B9H11]−
by Dmitriy K. Semyonov, Marina Yu. Stogniy, Kyrill Yu. Suponitsky and Igor B. Sivaev
Inorganics 2023, 11(3), 127; https://doi.org/10.3390/inorganics11030127 - 17 Mar 2023
Cited by 1 | Viewed by 1169
Abstract
New carboranyl thioethers 1-MeO(CH2)nS-1,2-C2B10H11 (n = 2, 3) were prepared by the alkylation of the trimethylammonium salt of 1-mercapto-ortho-carborane with 1-bromo- 2-methoxyethane and 1-bromo-3-methoxypropane, respectively. Their deboronation with cesium fluoride in ethanol [...] Read more.
New carboranyl thioethers 1-MeO(CH2)nS-1,2-C2B10H11 (n = 2, 3) were prepared by the alkylation of the trimethylammonium salt of 1-mercapto-ortho-carborane with 1-bromo- 2-methoxyethane and 1-bromo-3-methoxypropane, respectively. Their deboronation with cesium fluoride in ethanol gave the corresponding nido-carboranes Cs[7-MeO(CH2)nS-7,8-C2B9H11] (n = 2, 3). The reactions of Cs[7-MeO(CH2)2S-7,8-C2B9H11] with various nickel(II) phosphine complexes [(dppe)NiCl2] and [(R’R2P)2NiCl2] (R = R’ = Ph, Bu; R = Me, R’ = Ph; R = Ph, R’ = Me, Et) were studied and a series of nickelacarboranes 3,3-dppe-1-MeO(CH2)2S-closo-3,1,2-NiC2B9H10 and 3,3- (R’R2P)2-1-MeO(CH2)2S-closo-3,1,2-NiC2B9H10 (R = R’ = Bu; R = Me, R’ = Ph; R = Ph, R’ = Me, Et) was prepared. The molecular crystal structure of 3,3-dppe-1-MeO(CH2)2S-closo-3,1,2-NiC2B9H10 was determined by single-crystal X-ray diffraction. Full article
(This article belongs to the Special Issue Bioactivity of Transition Metal-Based Complexes)
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14 pages, 12871 KiB  
Article
A Graphene Oxide-Angiogenin Theranostic Nanoplatform for the Therapeutic Targeting of Angiogenic Processes: The Effect of Copper-Supplemented Medium
by Lorenzo Riela, Lorena Maria Cucci, Örjan Hansson, Tiziano Marzo, Diego La Mendola and Cristina Satriano
Inorganics 2022, 10(11), 188; https://doi.org/10.3390/inorganics10110188 - 29 Oct 2022
Cited by 3 | Viewed by 1479
Abstract
Graphene oxide (GO) nanosheets with different content in the defective carbon species bound to oxygen sp3 were functionalized with the angiogenin (ANG) protein, to create a novel nanomedicine for modulating angiogenic processes in cancer therapies. The GO@ANG nanocomposite was scrutinized utilizing UV-visible and [...] Read more.
Graphene oxide (GO) nanosheets with different content in the defective carbon species bound to oxygen sp3 were functionalized with the angiogenin (ANG) protein, to create a novel nanomedicine for modulating angiogenic processes in cancer therapies. The GO@ANG nanocomposite was scrutinized utilizing UV-visible and fluorescence spectroscopies. GO exhibits pro- or antiangiogenic effects, mostly attributed to the disturbance of ROS concentration, depending both on the total concentration (i.e., >100 ng/mL) as well as on the number of carbon species oxidized, that is, the C/O ratio. ANG is considered one of the most effective angiogenic factors that plays a vital role in the angiogenic process, often in a synergic role with copper ions. Based on these starting hypotheses, the GO@ANG nanotoxicity was assessed with the MTT colorimetric assay, both in the absence and in the presence of copper ions, by in vitro cellular experiments on human prostatic cancer cells (PC-3 line). Laser confocal microscopy (LSM) cell imaging evidenced an enhanced internationalization of GO@ANG than bare GO nanosheets, as well as significant changes in cell cytoskeleton organization and mitochondrial staining compared to the cell treatments with free ANG. Full article
(This article belongs to the Special Issue Bioactivity of Transition Metal-Based Complexes)
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15 pages, 2536 KiB  
Article
Pseudo-Tetrahedral Copper(I) Symmetrical Formamidine Dithiocarbamate-Phosphine Complexes: Antibacterial, Antioxidant and Pharmacokinetics Studies
by Segun D. Oladipo and Bernard Omondi
Inorganics 2022, 10(6), 79; https://doi.org/10.3390/inorganics10060079 - 10 Jun 2022
Cited by 4 | Viewed by 1693
Abstract
Three copper(I) dithiocarbamate–phosphine complexes of the general formula Cu(PPh3)2L were synthesized by metathesis reactions of the potassium salt of the dithiocarbamate ligand L and the precursor complex Cu(PPh3)2NO3 in an equimolar ratio. L represents [...] Read more.
Three copper(I) dithiocarbamate–phosphine complexes of the general formula Cu(PPh3)2L were synthesized by metathesis reactions of the potassium salt of the dithiocarbamate ligand L and the precursor complex Cu(PPh3)2NO3 in an equimolar ratio. L represents N,N′-bis(2,6-dimethylphenyl)formamidine dithiocarbamate L1 in complex 1, N,N′-bis(2,6-disopropylphenyl) formamidine dithiocarbamate L2 in complex 2, and N,N′-dimesitylformamidine dithiocarbamate L3 in complex 3. The single-crystal X-ray structure revealed the coordination of the copper atom to two sulfur atoms of the dithiocarbamates, as well as two phosphorus atoms of the PPh3 units, which resulted in distorted tetrahedral geometries. The calculated τ4 (tau factor) values for 1, 2 and 3 were 0.82, 0.81 and 0.85, respectively, confirming the pseudo-tetrahedral geometry proposed. Complexes 1–3 showed remarkable luminescent properties in CH2Cl2 at room temperature. All three complexes showed moderate-to-low antibacterial potential against Gram-negative bacteria, while none of the complexes were active against Gram-positive bacteria. The DPPH assay studies showed that complex 2 had the lowest IC50 (4.99 × 10−3 mM),and had higher DPPH free radical scavenging ability than 1 and 3. The pharmacological estimations of 1–3 showed that all of the complexes showed minimal violation of Lipinski’s rule. Full article
(This article belongs to the Special Issue Bioactivity of Transition Metal-Based Complexes)
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Review

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30 pages, 3363 KiB  
Review
The Role of Complexes of Biogenic Metals in Living Organisms
by Irena Kostova
Inorganics 2023, 11(2), 56; https://doi.org/10.3390/inorganics11020056 - 25 Jan 2023
Cited by 13 | Viewed by 2593
Abstract
Biogenic metals and their various inorganic, organometallic, and coordination compounds are comprehensively studied and extensively used in medical practice. Since the biogenic metals have various chemical properties corresponding to their position in the periodic table, their biological functions are different. Almost all of [...] Read more.
Biogenic metals and their various inorganic, organometallic, and coordination compounds are comprehensively studied and extensively used in medical practice. Since the biogenic metals have various chemical properties corresponding to their position in the periodic table, their biological functions are different. Almost all of the discussed biogenic elements have an ability to form coordination complexes. Furthermore, the different accessible oxidation states occupied by most of these elements enables the body to catalyze oxy-reduction interactions, depending on the biological conditions. As they are biogenic in nature, their deficiency or their excess in the body leads to numerous pathological obstructions. The application of metal-based compounds as medications is connected with the oxy-reduction properties and the capability to form coordination complexes, which are involved in many bioreactions. The usefulness of these metals as therapeutic and diagnostic agents is also pointed out. Full article
(This article belongs to the Special Issue Bioactivity of Transition Metal-Based Complexes)
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