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Inorganics
Special Issues
Metal-Based Anticancer Drugs
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Metal-Based Anticancer Drugs

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

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 17734

Special Issue Editors

Prof. Dr. Vladimir Arion

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Guest Editor
Institute of Inorganic Chemistry, University of Vienna, Währinger Str. 42, 1090 Vienna, Austria
Interests: coordination and bioinorganic chemistry, more specifically development of metal-based anticancer drugs based on isomeric indoloquinolines, indolobenzazepines, indolobenzazocines and indolobenzazonines, as well as on thiosemicarbazones; ruthenium-nitrosyl complexes with heterocyclic azoles as NO-releasing molecules and potential aniticancer drugs; bis-(thio)semicarbazide macrocyclic complexes as catalysts in alkane oxidation; transition metal complexes with noninnocent open-chain ligands
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Debbie Crans

E-Mail Website
Guest Editor
Department of Chemistry, Colorado State University, Fort Colllins, CO 80523, USA
Interests: biological, bioinorganic, bioorganic and bioanalytical chemistries; drugs for diseases such as tuberculosis, Alzheimer’s diabetes and cancer; organic drugs and transition metal-based drugs; menaquinone, pyrazinamide, metformin, platinum and vanadium derivatives; lipid systems and micro-emulsion environments
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ignacio E. Leon

E-Mail Website
Guest Editor
Centro de Química Inorgánica (CEQUINOR), CONICET‐UNLP, La Plata, Buenos Aires, Argentina
Interests: metal-based drugs; anticancer compounds; antimicrobial compounds; medicinal inorganic chemistry; copper, ruthenium, vanadium and platinum complexes; nanoparticles; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The use of metal complexes as anticancer agents revolutionized cancer treatment more than fifty years ago with the discovery of cisplatin, cis-[PtCl2(NH3)2]. Further research led to clinical use of other platinum drugs, namely, carboplatin and oxaliplatin. The main deficiencies of the platinum-based drugs are their severe side effects and drug resistance. New metal-based anticancer drugs including essential and nonessential metals that have a different mode of action might be able to broaden the spectrum of treatable cancers, reduce toxic side effects, and overcome platinum resistance. The concept of selective targeting of cancer cells remains a challenge. Many new approaches to the design of innovative metal-based anticancer drugs are currently emerging. These include prodrugs, dual or multi-action prodrugs, etc. Even though the chemistry of metal-based drugs has made considerable progress, there are other drawbacks such as poor aqueous solubility and pharmacological issues. To enhance the efficacy of new metal-based drugs, prodrug and targeting strategies, as well as suitable drug delivery approaches, are being developed (design and synthesis of new ligands, nanocarriers, etc.). The importance of studies into the underlying mechanisms of action, which have led to new molecular targets for metal-based drugs, is also increasing. This Special Issue aims to highlight the progress in the field of development of new metal-based anticancer drugs.

Prof. Dr. Vladimir Arion
Prof. Dr. Debbie C. Crans
Prof. Dr. Ignacio E. Leon
Guest Editors

Manuscript Submission Information

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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

  • anticancer metallodrugs
  • antimicrobial compounds
  • drug delivery
  • nanocarriers
  • drugs and biologically active compounds
  • pharmaceutically active compounds
  • metals in medicine

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Published Papers (4 papers)

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Research

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22 pages, 3358 KiB  
Article
Exploring Growth of Mycobacterium smegmatis Treated with Anticarcinogenic Vanadium Compounds
by Zeyad Arhouma, Heide A. Murakami, Jordan T. Koehn, Xiaorong Li, Deborah A. Roess, Dean C. Crick and Debbie C. Crans
Inorganics 2022, 10(4), 50; https://doi.org/10.3390/inorganics10040050 - 2 Apr 2022
Cited by 9 | Viewed by 2875
Abstract
A major problem with patient treatments using anticancer compounds is accompanying bacterial infections, which makes more information on how such compounds impact bacterial growth desirable. In the following study, we investigated the growth effects of an anticancerous non-toxic Schiff base oxidovanadium(V) complex ( [...] Read more.
A major problem with patient treatments using anticancer compounds is accompanying bacterial infections, which makes more information on how such compounds impact bacterial growth desirable. In the following study, we investigated the growth effects of an anticancerous non-toxic Schiff base oxidovanadium(V) complex (N-(salicylideneaminato)-N′-(2-hydroxyethyl)ethane-1,2-diamine) coordinated to the 3,5-di-tert-butylcatecholato ligand on a representative bacterium, Mycobacterium smegmatis (M. smeg). We prepared the Schiff base V-complexes as reported previously and selected a few complexes to develop a V-complex series. Biological studies of M. smeg growth inhibition were complemented by spectroscopic studies using UV-Vis spectrophotometry and NMR spectroscopy to determine which complexes were intact under biologically relevant conditions. We specifically chose to examine (1) the growth effects of Schiff base oxidovanadium complexes coordinated to a catechol, (2) the growth effects of respective free catecholates on M. smeg, and (3) to identify complexes where the metal coordination complex was more potent than the ligand alone under biological conditions. Results from these studies showed that the observed effects of Schiff base V-catecholate complex are a combination of catechol properties including toxicity, hydrophobicity, and sterics. Full article
(This article belongs to the Special Issue Metal-Based Anticancer Drugs)
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16 pages, 2182 KiB  
Article
Synthesis and Characterization of Novel Copper(II)-Sunitinib Complex: Molecular Docking, DFT Studies, Hirshfeld Analysis and Cytotoxicity Studies
by Facundo Tarasi, Priscila Ailín Lanza, Valeria Ferretti, Gustavo Alberto Echeverría, Oscar Enrique Piro, Maximiliano Cacicedo, Stephan Gehring, Ignacio Esteban León and María Soledad Islas
Inorganics 2022, 10(1), 3; https://doi.org/10.3390/inorganics10010003 - 22 Dec 2021
Cited by 3 | Viewed by 3270
Abstract
The main goal of this work was to report the synthesis, characterization, and cytotoxicity study of a novel copper(II)-sunitinib complex, CuSun. It has been synthesized and characterized in solid state and in solution by different methods (such as DFT, FTIR, Raman, UV-vis, EPR, [...] Read more.
The main goal of this work was to report the synthesis, characterization, and cytotoxicity study of a novel copper(II)-sunitinib complex, CuSun. It has been synthesized and characterized in solid state and in solution by different methods (such as DFT, FTIR, Raman, UV-vis, EPR, NMR, etc.). The solid-state molecular structure of trichlorosunitinibcopper(II), where sunitinib: N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, for short Cu(Sun)Cl3, was determined by X-ray diffraction. It crystallizes in the triclinic space group P-1 with a = 7.9061(5) Å, b = 12.412(1) Å, c = 13.7005(8) Å, α = 105.021(6)°, β = 106.744(5)°, γ = 91.749(5)°, and Z = 2 molecules per unit cell. Also, we have found π-π interactions and classic and non-classic H-bonds in the crystal structure by using Hirshfeld surface analysis. In the speciation studies, the complex has dissociated in protonated sunitinib and chlorocomplex of copper(II), according to 1HNMR, EPR, UV-vis and conductimetric analysis. Molecular docking of the complex in both, ATP binding site and allosteric site of VEGFR2 have shown no improvement in comparison to the free ligand. Besides, cytotoxicity assay on HepG2 cell line shows similar activity for complex and ligand in the range between 1–25 μM supporting the data obtained from studies in solution. Full article
(This article belongs to the Special Issue Metal-Based Anticancer Drugs)
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15 pages, 2499 KiB  
Article
Synthesis, Crystal Structure, Spectroscopic Characterization, DFT Calculations and Cytotoxicity Assays of a New Cu(II) Complex with an Acylhydrazone Ligand Derived from Thiophene
by María R. Rodríguez, Lucía M. Balsa, Oscar E. Piro, Gustavo A. Etcheverría, Javier García-Tojal, Reinaldo Pis-Diez, Ignacio E. León, Beatriz P. Parajón-Costa and Ana C. González-Baró
Inorganics 2021, 9(2), 9; https://doi.org/10.3390/inorganics9020009 - 20 Jan 2021
Cited by 19 | Viewed by 3497
Abstract
A new Cu(II) complex is synthetized by the reaction of copper nitrate and a N-acylhydrazone ligand obtained from the condensation of o-vanillin and 2-thiophecarbohydrazide (H2L). The solid-state structure of [Cu(HL)(H2O)](NO3)·H2O, or CuHL for [...] Read more.
A new Cu(II) complex is synthetized by the reaction of copper nitrate and a N-acylhydrazone ligand obtained from the condensation of o-vanillin and 2-thiophecarbohydrazide (H2L). The solid-state structure of [Cu(HL)(H2O)](NO3)·H2O, or CuHL for simplicity, was determined by X-ray diffraction. In the cationic complex, the copper center is in a nearly squared planar environment with the nitrate interacting as a counterion. CuHL was characterized by spectroscopic techniques, including solid-state FTIR, Raman, electron paramagnetic resonance (EPR) and diffuse reflectance and solution UV-Vis electronic spectroscopy. Calculations based on the density functional theory (DFT) assisted the interpretation and assignment of the spectroscopic data. The complex does not show relevant antioxidant activity evaluated by the radical cation of 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) method, being even less active than the free ligand as a radical quencher. Cytotoxicity assays of CuHL against three human tumor cell lines, namely MG-63, A549 and HT-29, revealed an important enhancement of the effectiveness as compared with both the ligand and the free metal ion. Moreover, its cytotoxic effect was remarkably stronger than that of the reference metallodrug cisplatin in all cancer cell lines tested, a promissory result in the search for new metallodrugs of essential transition metals. Full article
(This article belongs to the Special Issue Metal-Based Anticancer Drugs)
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Review

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28 pages, 6103 KiB  
Review
Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug
by Louis J. Delinois, Omar De León-Vélez, Adriana Vázquez-Medina, Alondra Vélez-Cabrera, Amanda Marrero-Sánchez, Christopher Nieves-Escobar, Daniela Alfonso-Cano, Delvin Caraballo-Rodríguez, Jael Rodriguez-Ortiz, Jemily Acosta-Mercado, Josué A. Benjamín-Rivera, Kiara González-González, Kysha Fernández-Adorno, Lisby Santiago-Pagán, Rafael Delgado-Vergara, Xaiomy Torres-Ávila, Andrea Maser-Figueroa, Gladimarys Grajales-Avilés, Glorimar I. Miranda Méndez, Javier Santiago-Pagán, Miguel Nieves-Santiago, Vanessa Álvarez-Carrillo, Kai Griebenow and Arthur D. Tinocoadd Show full author list remove Hide full author list
Inorganics 2021, 9(11), 83; https://doi.org/10.3390/inorganics9110083 - 16 Nov 2021
Cited by 10 | Viewed by 5809
Abstract
The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic [...] Read more.
The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market. Full article
(This article belongs to the Special Issue Metal-Based Anticancer Drugs)
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