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Journal articles on the topic 'ANTICANCER METALLODRUG'

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Author: Grafiati

Published: 10 March 2023

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1

Sullivan, Matthew P., Michael Groessl, Samuel M. Meier, Richard L. Kingston, David C. Goldstone, and Christian G. Hartinger. "The metalation of hen egg white lysozyme impacts protein stability as shown by ion mobility mass spectrometry, differential scanning calorimetry, and X-ray crystallography." Chemical Communications 53, no. 30 (2017): 4246–49. http://dx.doi.org/10.1039/c6cc10150j.

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2

Hartinger, Christian G., and Bernhard K. Keppler. "CE in anticancer metallodrug research – an update." ELECTROPHORESIS 28, no. 19 (October 2007): 3436–46. http://dx.doi.org/10.1002/elps.200700114.

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3

Páez-Franco, José C., Miriam R. Zermeño-Ortega, Carmen Myriam de la O-Contreras, Daniel Canseco-González, Jesus R. Parra-Unda, Alcives Avila-Sorrosa, Raúl G. Enríquez, Juan M. Germán-Acacio, and David Morales-Morales. "Relevance of Fluorinated Ligands to the Design of Metallodrugs for Their Potential Use in Cancer Treatment." Pharmaceutics 14, no. 2 (February 11, 2022): 402. http://dx.doi.org/10.3390/pharmaceutics14020402.

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Fluorination of pharmaceutical agents has afforded crucial modifications to their pharmacological profiles, leading to important advances in medicinal chemistry. On the other hand, metallodrugs are considered to be valuable candidates in the treatment of several diseases, albeit with the caveat that they may exhibit pharmacological disadvantages, such as poor water solubility, low bioavailability and short circulating time. To surmount these limitations, two approaches have been developed: one based on the design of novel metallodrug-delivering carriers and the other based on optimizing the structure of the ligands bound to the metal center. In this context, fluorination of the ligands may bring beneficial changes (physicochemical and biological) that can help to elude the aforementioned drawbacks. Thus, in this review, we discuss the use of fluorinated ligands in the design of metallodrugs that may exhibit potential anticancer activity.

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4

Steel, Tasha R., and Christian G. Hartinger. "Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs." Metallomics 12, no. 11 (2020): 1627–36. http://dx.doi.org/10.1039/d0mt00196a.

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5

Doroudian, Maryam, and Jürgen Gailer. "Integrative Metallomics Studies of Toxic Metal(loid) Substances at the Blood Plasma–Red Blood Cell–Organ/Tumor Nexus." Inorganics 10, no. 11 (November 7, 2022): 200. http://dx.doi.org/10.3390/inorganics10110200.

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Globally, an estimated 9 million deaths per year are caused by human exposure to environmental pollutants, including toxic metal(loid) species. Since pollution is underestimated in calculations of the global burden of disease, the actual number of pollution-related deaths per year is likely to be substantially greater. Conversely, anticancer metallodrugs are deliberately administered to cancer patients, but their often dose-limiting severe adverse side-effects necessitate the urgent development of more effective metallodrugs that offer fewer off-target effects. What these seemingly unrelated events have in common is our limited understanding of what happens when each of these toxic metal(loid) substances enter the human bloodstream. However, the bioinorganic chemistry that unfolds at the plasma/red blood cell interface is directly implicated in mediating organ/tumor damage and, therefore, is of immediate toxicological and pharmacological relevance. This perspective will provide a brief synopsis of the bioinorganic chemistry of AsIII, Cd2+, Hg2+, CH3Hg+ and the anticancer metallodrug cisplatin in the bloodstream. Probing these processes at near-physiological conditions and integrating the results with biochemical events within organs and/or tumors has the potential to causally link chronic human exposure to toxic metal(loid) species with disease etiology and to translate more novel anticancer metal complexes to clinical studies, which will significantly improve human health in the 21st century.

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Karas, Brittany F., Jordan M. Hotz, Brian M. Gural, Kristin R. Terez, Victoria L. DiBona, Leonor Côrte-Real, Andreia Valente, Brian T. Buckley, and Keith R. Cooper. "Anticancer Activity and In Vitro to In Vivo Mechanistic Recapitulation of Novel Ruthenium-Based Metallodrugs in the Zebrafish Model." Toxicological Sciences 182, no. 1 (April 3, 2021): 29–43. http://dx.doi.org/10.1093/toxsci/kfab041.

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Abstract Ruthenium is popular as a metal core for chemotherapeutics, due to versatile molecular coordination. Because new metallodrugs are synthesized at high rates, our studies included assays in zebrafish to expedite the initial evaluation as anticancer agents. Here we evaluated novel metallodrugs (PMC79 and LCR134), and cisplatin, a widely used platinum-based chemotherapeutic. We hypothesized that this model could characterize anticancer properties and recapitulate previous in vitro results in vivo. Our findings suggest anticancer properties of PMC79 and LCR134 were similar with less toxicity than cisplatin. Exposures from 24 to 72 h at or below the LOAELs of PMC79 and LCR134 (3.9 µM and 13.5 µm, respectively), impaired blood vessel development and tailfin regeneration. Blood vessel examination through live imaging of larvae revealed distinct regional antiangiogenic impacts. The significant decrease in gene expression of the VEGF-HIF pathway and beta-actin could explain the morphological effects observed in the whole organism following exposure. Tailfin amputation in larvae exposed to PMC79 or LCR134 inhibited tissue regrowth and cell division, but did not impact normal cell proliferation unlike cisplatin. This suggests Ru drugs may be more selective in targeting cancerous cells than cisplatin. Additionally, in vitro mechanisms were confirmed. PMC79 disrupted cytoskeleton formation in larvae and P-glycoprotein transporters in vivo was inhibited at low doses which could limit off-target effects of chemotherapeutics. Our results demonstrate the value for using the zebrafish in metallodrug research to evaluate mechanisms and off-target effects. In light of the findings reported in this article, future investigation of PMC79 and LCR134 are warranted in higher vertebrate models.

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7

Monti, Daria Maria, Domenico Loreto, Ilaria Iacobucci, Giarita Ferraro, Alessandro Pratesi, Luigi D’Elia, Maria Monti, and Antonello Merlino. "Protein-Based Delivery Systems for Anticancer Metallodrugs: Structure and Biological Activity of the Oxaliplatin/β-Lactoglobulin Adduct." Pharmaceuticals 15, no. 4 (March 30, 2022): 425. http://dx.doi.org/10.3390/ph15040425.

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β-lactoglobulin is the major component of whey. Here, the adduct formed upon the reaction of the protein with oxaliplatin (OXA) has been prepared, structurally characterized by X-ray crystallography and electrospray ionization–mass spectrometry, and evaluated as a cytotoxic agent. The data demonstrate that OXA rapidly binds β-lactoglobulin via coordination with a Met7 side chain upon release of the oxalate ligand. The adduct is significantly more cytotoxic than the free drug and induces apoptosis in cancer cells. Overall, our results suggest that metallodrug/β-lactoglobulin adducts can be used as anticancer agents and that the protein can be used as a metallodrug delivery system.

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8

Holtkamp, Hannah U., and Christian G. Hartinger. "Advanced metallomics methods in anticancer metallodrug mode of action studies." TrAC Trends in Analytical Chemistry 104 (July 2018): 110–17. http://dx.doi.org/10.1016/j.trac.2017.09.023.

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9

Monti, Dara Maria, Giarita Ferraro, and Antonello Merlino. "Ferritin-based anticancer metallodrug delivery: Crystallographic, analytical and cytotoxicity studies." Nanomedicine: Nanotechnology, Biology and Medicine 20 (August 2019): 101997. http://dx.doi.org/10.1016/j.nano.2019.04.001.

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10

Artner, Christian, Hannah U. Holtkamp, Wolfgang Kandioller, Christian G. Hartinger, Samuel M. Meier-Menches, and Bernhard K. Keppler. "DNA or protein? Capillary zone electrophoresis–mass spectrometry rapidly elucidates metallodrug binding selectivity." Chemical Communications 53, no. 57 (2017): 8002–5. http://dx.doi.org/10.1039/c7cc04582d.

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11

Timerbaev, A. R., K. Pawlak, C. Gabbiani, and L. Messori. "Recent progress in the application of analytical techniques to anticancer metallodrug proteomics." TrAC Trends in Analytical Chemistry 30, no. 7 (July 2011): 1120–38. http://dx.doi.org/10.1016/j.trac.2011.03.007.

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12

Hackl, Carmen M., Beatrix Schoenhacker-Alte, Matthias H. M. Klose, Helena Henke, Maria S. Legina, Michael A. Jakupec, Walter Berger, et al. "Synthesis and in vivo anticancer evaluation of poly(organo)phosphazene-based metallodrug conjugates." Dalton Transactions 46, no. 36 (2017): 12114–24. http://dx.doi.org/10.1039/c7dt01767g.

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13

Groessl, Michael, and Christian G. Hartinger. "Anticancer metallodrug research analytically painting the “omics” picture—current developments and future trends." Analytical and Bioanalytical Chemistry 405, no. 6 (October 16, 2012): 1791–808. http://dx.doi.org/10.1007/s00216-012-6450-4.

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14

Miller, Maya, Anna Mellul, Maya Braun, Dana Sherill-Rofe, Emiliano Cohen, Zohar Shpilt, Irene Unterman, et al. "Titanium Tackles the Endoplasmic Reticulum: A First Genomic Study on a Titanium Anticancer Metallodrug." iScience 23, no. 7 (July 2020): 101262. http://dx.doi.org/10.1016/j.isci.2020.101262.

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15

Demoro, Bruno, Andreia Bento-Oliveira, Fernanda Marques, João Costa Pessoa, Lucía Otero, Dinorah Gambino, Rodrigo F. M. de Almeida, and Ana Isabel Tomaz. "Interaction with Blood Proteins of a Ruthenium(II) Nitrofuryl Semicarbazone Complex: Effect on the Antitumoral Activity." Molecules 24, no. 16 (August 7, 2019): 2861. http://dx.doi.org/10.3390/molecules24162861.

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The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic solutions. Given their high efficiency, metallodrugs are quite appealing in cancer chemotherapy. This work examined the anticancer activity of an anti-trypanosomal ruthenium-based compound bearing the 5-nitrofuryl pharmacophore, [RuII(dmso)2(5-nitro-2-furaldehyde semicarbazone)] (abbreviated as RuNTF; dmso is the dimethyl sulfoxide ligand). The cytotoxicity of RuNTF was evaluated in vitro against ovarian adenocarcinoma, hormone-dependent breast adenocarcinoma, prostate carcinoma (grade IV) and V79 lung fibroblasts human cells. The activity of RuNTF was similar to the benchmark metallodrug cisplatin for the breast line and inactive against the prostate line and lung fibroblasts. Given the known role of serum protein binding in drug bioavailability and the distribution via blood plasma, this study assessed the interaction of RuNTF with human serum albumin (HSA) by circular dichroism (CD) and fluorescence spectroscopy. The fluorescence emission quenching from the HSA-Trp214 residue and the lifetime data upon RuNTF binding evidenced the formation of a 1:1 {RuNTF-albumin} adduct with log Ksv = (4.58 ± 0.01) and log KB = (4.55 ± 0.01). This is supported by CD data with an induced CD broad band observed at ~450 nm even after short incubation times. Importantly, the binding to either HSA or human apo-transferrin is beneficial to the cytotoxicity of the complex towards human cancer cells by enhancing the cytotoxic activity of RuNTF.

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16

Oliveira, Katia M., João Honorato, Felipe C. Demidoff, Mario S. Schultz, Chaquip D. Netto, Marcia R. Cominetti, Rodrigo S. Correa, and Alzir A. Batista. "Lapachol in the Design of a New Ruthenium(II)-Diphosphine Complex as a Promising Anticancer Metallodrug." Journal of Inorganic Biochemistry 214 (January 2021): 111289. http://dx.doi.org/10.1016/j.jinorgbio.2020.111289.

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17

Ugalde-Arbizu, Maider, John Jairo Aguilera-Correa, Victoria García-Almodóvar, Karina Ovejero-Paredes, Diana Díaz-García, Jaime Esteban, Paulina L. Páez, et al. "Dual Anticancer and Antibacterial Properties of Silica-Based Theranostic Nanomaterials Functionalized with Coumarin343, Folic Acid and a Cytotoxic Organotin(IV) Metallodrug." Pharmaceutics 15, no. 2 (February 7, 2023): 560. http://dx.doi.org/10.3390/pharmaceutics15020560.

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Five different silica nanoparticles functionalized with vitamin B12, a derivative of coumarin found in green plants and a minimum content of an organotin(IV) fragment (1-MSN-Sn, 2-MSN-Sn, 2-SBA-Sn, 2-FSPm-Sn and 2-FSPs-Sn), were identified as excellent anticancer agents against triple negative breast cancer, one of the most diagnosed and aggressive cancerous tumors, with very poor prognosis. Notably, compound 2-MSN-Sn shows selectivity for cancer cells and excellent luminescent properties detectable by imaging techniques once internalized. The same compound is also able to interact with and nearly eradicate biofilms of Staphylococcus aureus, the most common bacteria isolated from chronic wounds and burns, whose treatment is a clinical challenge. 2-MSN-Sn is efficiently internalized by bacteria in a biofilm state and destroys the latter through reactive oxygen species (ROS) generation. Its internalization by bacteria was also efficiently monitored by fluorescence imaging. Since silica nanoparticles are particularly suitable for oral or topical administration, and considering both its anticancer and antibacterial activity, 2-MSN-Sn represents a new dual-condition theranostic agent, based primarily on natural products or their derivatives and with only a minimum amount of a novel metallodrug.

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18

Kljun, Jakob, and Iztok Turel. "β-Diketones as Scaffolds for Anticancer Drug Design - From Organic Building Blocks to Natural Products and Metallodrug Components." European Journal of Inorganic Chemistry 2017, no. 12 (February 16, 2017): 1655–66. http://dx.doi.org/10.1002/ejic.201601314.

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19

Côrte-Real, Leonor, António P. Matos, Irina Alho, Tânia S. Morais, Ana Isabel Tomaz, Maria Helena Garcia, Isabel Santos, Manuel P. Bicho, and Fernanda Marques. "Cellular Uptake Mechanisms of an Antitumor Ruthenium Compound: The Endosomal/Lysosomal System as a Target for Anticancer Metal-Based Drugs." Microscopy and Microanalysis 19, no. 5 (June 24, 2013): 1122–30. http://dx.doi.org/10.1017/s143192761300175x.

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AbstractPrevious studies have described promising antitumor activity of an organometallic Ru(II) complex, η5-Cyclopentadienyl(2,2′-bipyridyl)(triphenylphosphane) Ruthenium(II) triflate ([(η5-C5H5)Ru(2,2′-bipyridyl)(PPh3)][CF3SO3]) herein designated as TM34. Its broad spectrum of activity against a panel of human tumor cell lines and high antiproliferative efficiency prompted us to focus on its mode of action. We present herein results obtained with two human tumor cell lines A2780 and MDAMB231 on the compound distribution within the cell, the mechanism of its activity, and its cellular targets. The prospective metallodrug TM34 revealed: (a) fast antiproliferative effects even at short incubation times for both cell lines; (b) preferential localization at the cell membrane and cytosol; (c) cellular activity by a temperature-dependent process, probably macropinocytosis; (d) inhibition of a lysosomal enzyme, acid phosphatase, in a dose-dependent mode; and (e) disruption and vesiculation of the Golgi apparatus, which suggest the involvement of the endosomal/lysosomal system in its mode of action. These results are essential to elucidate the basis for the cytotoxic activity and mechanism of action of this RuII(η5-cyclopentadienyl) complex.

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20

Jarosz, Maciej, Magdalena Matczuk, Katarzyna Pawlak, and Andrei R. Timerbaev. "Molecular mass spectrometry in metallodrug development: A case of mapping transferrin-mediated transformations for a ruthenium(III) anticancer drug." Analytica Chimica Acta 851 (December 2014): 72–77. http://dx.doi.org/10.1016/j.aca.2014.08.031.

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21

Casini, Angela, Chiara Gabbiani, Guido Mastrobuoni, Luigi Messori, Gloriano Moneti, and Giuseppe Pieraccini. "Exploring Metallodrug–Protein Interactions by ESI Mass Spectrometry: The Reaction of Anticancer Platinum Drugs with Horse Heart Cytochrome c." ChemMedChem 1, no. 4 (April 10, 2006): 413–17. http://dx.doi.org/10.1002/cmdc.200500079.

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22

Yu, Zhen, Menglu Han, and James A. Cowan. "Toward the Design of a Catalytic Metallodrug: Selective Cleavage of G-Quadruplex Telomeric DNA by an Anticancer Copper-Acridine-ATCUN Complex." Angewandte Chemie 127, no. 6 (December 12, 2014): 1921–25. http://dx.doi.org/10.1002/ange.201410434.

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23

Yu, Zhen, Menglu Han, and James A. Cowan. "Toward the Design of a Catalytic Metallodrug: Selective Cleavage of G-Quadruplex Telomeric DNA by an Anticancer Copper-Acridine-ATCUN Complex." Angewandte Chemie International Edition 54, no. 6 (December 11, 2014): 1901–5. http://dx.doi.org/10.1002/anie.201410434.

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24

Marson Armando, Renan Augusto, Marina Paiva Abuçafy, Angelica Ellen Graminha, Roberto Santana da Silva, and Regina Célia Galvão Frem. "Ru-90@bio-MOF-1: A ruthenium(II) metallodrug occluded in porous Zn-based MOF as a strategy to develop anticancer agents." Journal of Solid State Chemistry 297 (May 2021): 122081. http://dx.doi.org/10.1016/j.jssc.2021.122081.

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25

Dantas, Kele Cristina Ferreira, Jânia dos Santos Rosário, and Priscila Pereira Silva-Caldeira. "Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements." Pharmaceutics 14, no. 7 (July 20, 2022): 1506. http://dx.doi.org/10.3390/pharmaceutics14071506.

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Nanotechnology-based approaches for targeting the delivery and controlled release of metal-based therapeutic agents have revealed significant potential as tools for enhancing the therapeutic effect of metal-based agents and minimizing their systemic toxicities. In this context, a series of polymer-based nanosized systems designed to physically load or covalently conjugate metal-based therapeutic agents have been remarkably improving their bioavailability and anticancer efficacy. Initially, the polymeric nanocarriers were applied for platinum-based chemotherapeutic agents resulting in some nanoformulations currently in clinical tests and even in medical applications. At present, these nanoassemblies have been slowly expanding for nonplatinum-containing metal-based chemotherapeutic agents. Interestingly, for metal-based photosensitizers (PS) applied in photodynamic therapy (PDT), especially for cancer treatment, strategies employing polymeric nanocarriers have been investigated for almost 30 years. In this review, we address the polymeric nanocarrier-assisted metal-based therapeutics agent delivery systems with a specific focus on non-platinum systems; we explore some biological and physicochemical aspects of the polymer–metallodrug assembly. Finally, we summarize some recent advances in polymeric nanosystems coupled with metal-based compounds that present potential for successful clinical applications as chemotherapeutic or photosensitizing agents. We hope this review can provide a fertile ground for the innovative design of polymeric nanosystems for targeting the delivery and controlled release of metal-containing therapeutic agents.

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Nešić, Maja D., Tanja Dučić, Manuel Algarra, Iva Popović, Milutin Stepić, Mara Gonçalves, and Marijana Petković. "Lipid Status of A2780 Ovarian Cancer Cells after Treatment with Ruthenium Complex Modified with Carbon Dot Nanocarriers: A Multimodal SR-FTIR Spectroscopy and MALDI TOF Mass Spectrometry Study." Cancers 14, no. 5 (February 24, 2022): 1182. http://dx.doi.org/10.3390/cancers14051182.

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In the last decade, targeting membrane lipids in cancer cells has been a promising approach that deserves attention in the field of anticancer drug development. To get a comprehensive understanding of the effect of the drug [Ru(η5-Cp)(PPh3)2CN] (RuCN) on cell lipidic components, we combine complementary analytical approaches, matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI TOF MS) and synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy. Techniques are used for screening the effect of potential metallodrug, RuCN, without and with drug carriers (carbon dots (CDs) and nitrogen-doped carbon dots (N-CDs)) on the lipids of the human ovarian cancer cell line A2780. MALDI TOF MS results revealed that the lysis of ovarian cancer membrane lipids is promoted by RuCN and not by drug carriers (CDs and N-CDs). Furthermore, SR-FTIR results strongly suggested that the phospholipids of cancer cells undergo oxidative stress after the treatment with RuCN that was accompanied by the disordering of the fatty acid chains. On the other hand, using (N-)CDs as RuCN nanocarriers prevented the oxidative stress caused by RuCN but did not prevent the disordering of the fatty acid chain packing. Finally, we demonstrated that RuCN and RuCN/(N-)CDs alter the hydration of the membrane surface in the membrane–water interface region.

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Liang, Wei, Junfeng Shi, Haiyan Xia, and Xiaowei Wei. "A Novel Ruthenium-Fluvastatin Complex Downregulates SNCG Expression to Modulate Breast Carcinoma Cell Proliferation and Apoptosis via Activating the PI3K/Akt/mTOR/VEGF/MMP9 Pathway." Oxidative Medicine and Cellular Longevity 2021 (June 6, 2021): 1–34. http://dx.doi.org/10.1155/2021/5537737.

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Breast cancer is the most common cause of malignancy and cancer-related morbidity and death worldwide that requests effective and safe chemotherapy. Evaluation of metallodrug-based anticancer agents and statins as chemotherapeutics with fewer side effects is a largely unexplored research field. Synthesis and characterization of the ruthenium-fluvastatin complex were achieved using multiple spectroscopic techniques and thus further examined to evaluate its chemotherapeutic prospects in both MDA-MB-231 and MCF-7 cancer lines and eventually in vivo models of DMBA-induced mammary carcinogenesis in rodents. Our studies indicate that the metal and ligand chelation was materialized by the ligand’s functional groups of carbonyl (=O) oxygen and hydroxyl (-OH), and the complex has been observed to be crystalline and able to chelate with CT-DNA. The complex was able to reduce cell proliferation and activate apoptotic events in breast carcinoma cell lines MCF-7 and MDA-MB-231. In addition, the complex was able to modify p53 expressions to interfere with apoptosis in the carcinoma of the breast, stimulated by the intrinsic apoptotic path assisted by Bcl2 and Bax in vivo, yet at the same point, controlling the PI3K/Akt/mTOR/VEGF pathway, as obtained from western blotting, correlates with the MMP9-regulated tumor mechanisms. Our research reveals that ruthenium-fluvastatin chemotherapy may disrupt, rescind, or interrupt breast carcinoma progression by modifying intrinsic apoptosis as well as the antiangiogenic cascade, thereby taking the role of a potential candidate in cancer therapy for the immediate future.

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Neuditschko, Benjamin, Anton A. Legin, Dina Baier, Arno Schintlmeister, Siegfried Reipert, Michael Wagner, Bernhard K. Keppler, Walter Berger, Samuel M. Meier‐Menches, and Christopher Gerner. "Inside Cover: Interaction with Ribosomal Proteins Accompanies Stress Induction of the Anticancer Metallodrug BOLD‐100/KP1339 in the Endoplasmic Reticulum (Angew. Chem. Int. Ed. 10/2021)." Angewandte Chemie International Edition 60, no. 10 (February 2021): 4954. http://dx.doi.org/10.1002/anie.202100977.

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Komeda, Seiji, and Angela Casini. "Next-Generation Anticancer Metallodrugs." Current Topics in Medicinal Chemistry 12, no. 3 (February 1, 2012): 219–35. http://dx.doi.org/10.2174/156802612799078964.

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30

Poursharifi, Mina, Marek T. Wlodarczyk, and Aneta J. Mieszawska. "Nano-Based Systems and Biomacromolecules as Carriers for Metallodrugs in Anticancer Therapy." Inorganics 7, no. 1 (December 20, 2018): 2. http://dx.doi.org/10.3390/inorganics7010002.

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Since the discovery of cisplatin and its potency in anticancer therapy, the development of metallodrugs has been an active area of research. The large choice of transition metals, oxidation states, coordinating ligands, and different geometries, allows for the design of metal-based agents with unique mechanisms of action. Many metallodrugs, such as titanium, ruthenium, gallium, tin, gold, and copper-based complexes have been found to have anticancer activities. However, biological application of these agents necessitates aqueous solubility and low systemic toxicity. This minireview highlights the emerging strategies to facilitate the in vivo application of metallodrugs, aimed at enhancing their solubility and bioavailability, as well as improving their delivery to tumor tissues. The focus is on encapsulating the metal-based complexes into nanocarriers or coupling to biomacromolecules, generating efficacious anticancer therapies. The delivery systems for complexes of platinum, ruthenium, copper, and iron are discussed with most recent examples.

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31

Sabounchei, Seyyed Javad, Marjan Hosseinzadeh, Sadegh Salehzadeh, Farahnaz Maleki, and Robert W. Gable. "Mononuclear palladium(ii) and platinum(ii) complexes of P,C-donor ligands: synthesis, crystal structures, cytotoxicity, and mechanistic studies of a highly stereoselective Mizoroki–Heck reaction." Inorganic Chemistry Frontiers 4, no. 12 (2017): 2107–18. http://dx.doi.org/10.1039/c7qi00568g.

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32

Broomfield, L. M., C. Alonso-Moreno, E. Martin, A. Shafir, I. Posadas, V. Ceña, and J. A. Castro-Osma. "Aminophosphine ligands as a privileged platform for development of antitumoral ruthenium(ii) arene complexes." Dalton Transactions 46, no. 46 (2017): 16113–25. http://dx.doi.org/10.1039/c7dt03369a.

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33

Máliková, Klaudia, Lukáš Masaryk, and Pavel Štarha. "Anticancer Half-Sandwich Rhodium(III) Complexes." Inorganics 9, no. 4 (April 8, 2021): 26. http://dx.doi.org/10.3390/inorganics9040026.

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Platinum-based anticancer drugs are most likely the most successful group of bioinorganic compounds. Their apparent disadvantages have led to the development of anticancer compounds of other noble metals, resulting in several ruthenium-based drugs which have entered clinical trials on oncological patients. Besides ruthenium, numerous rhodium complexes have been recently reported as highly potent antiproliferative agents against various human cancer cells, making them potential alternatives to Pt- and Ru-based metallodrugs. In this review, half-sandwich Rh(III) complexes are overviewed. Many representatives show higher in vitro potency than and different mechanisms of action (MoA) from the conventional anticancer metallodrugs (cisplatin in most cases) or clinically studied Ru drug candidates. Furthermore, some of the reviewed Rh(III) arenyl complexes are also anticancer in vivo. Pioneer anticancer organorhodium compounds as well as the recent advances in the field are discussed properly, and adequate attention is paid to their anticancer activity, solution behaviour and various processes connected with their MoA. In summary, this work summarizes the types of compounds and the most important biological results obtained in the field of anticancer half-sandwich Rh complexes.

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34

Schmidlehner, Melanie, Lea S. Flocke, Alexander Roller, Michaela Hejl, Michael A. Jakupec, Wolfgang Kandioller, and Bernhard K. Keppler. "Cytotoxicity and preliminary mode of action studies of novel 2-aryl-4-thiopyrone-based organometallics." Dalton Transactions 45, no. 2 (2016): 724–33. http://dx.doi.org/10.1039/c5dt02722e.

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35

Hanif, Muhammad, and Christian G. Hartinger. "Anticancer metallodrugs: where is the next cisplatin?" Future Medicinal Chemistry 10, no. 6 (March 2018): 615–17. http://dx.doi.org/10.4155/fmc-2017-0317.

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36

Ahmedova, Anife, Rositsa Mihaylova, Denitsa Momekova, Pavletta Shestakova, Silviya Stoykova, Joana Zaharieva, Masahiro Yamashina, Georgi Momekov, Munetaka Akita, and Michito Yoshizawa. "M2L4 coordination capsules with tunable anticancer activity upon guest encapsulation." Dalton Transactions 45, no. 33 (2016): 13214–21. http://dx.doi.org/10.1039/c6dt01801g.

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37

Spisz, Paulina, Agnieszka Chylewska, Aleksandra Królicka, Sandra Ramotowska, Aleksandra Dąbrowska, and Mariusz Makowski. "Stimulation of Sulfonamides Antibacterial Drugs Activity as a Result of Complexation with Ru(III): Physicochemical and Biological Study." International Journal of Molecular Sciences 22, no. 24 (December 15, 2021): 13482. http://dx.doi.org/10.3390/ijms222413482.

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Antibiotic resistance is a global problem, and one promising solution to overcome this issue is using metallodrugs, which are drugs containing metal ions and ligands. These complexes are superior to free ligands in various characteristics including anticancer properties and mechanism of action. The pharmacological potential of metallodrugs can be modulated by the appropriate selection of ligands and metal ions. A good example of proper coordination is the combination of sulfonamides (sulfamerazine, sulfathiazole) with a ruthenium(III) ion. This work aimed to confirm that the activity of sulfonamides antibacterial drugs is initiated and/or stimulated by their coordination to an Ru(III) ion. The study determined the structure, electrochemical profile, CT-DNA affinity, and antimicrobial as well as anticancer properties of the synthesized complexes. The results proved that Ru(III) complexes exhibited better biological properties than the free ligands.

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Ortega, Enrique, Gloria Vigueras, Francisco José Ballester, and José Ruiz. "Targeting translation: a promising strategy for anticancer metallodrugs." Coordination Chemistry Reviews 446 (November 2021): 214129. http://dx.doi.org/10.1016/j.ccr.2021.214129.

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Bagowski, Christoph P., Ya You, Heike Scheffler, Danielle H. Vlecken, Daan J. Schmitz, and Ingo Ott. "Naphthalimide gold(i) phosphine complexes as anticancer metallodrugs." Dalton Transactions, no. 48 (2009): 10799. http://dx.doi.org/10.1039/b912378d.

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Erxleben, Andrea. "Mitochondria-Targeting Anticancer Metal Complexes." Current Medicinal Chemistry 26, no. 4 (April 1, 2019): 694–728. http://dx.doi.org/10.2174/0929867325666180307112029.

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Background: Since the serendipitous discovery of the antitumor activity of cisplatin there has been a continuous surge in studies aimed at the development of new cytotoxic metal complexes. While the majority of these complexes have been designed to interact with nuclear DNA, other targets for anticancer metallodrugs attract increasing interest. In cancer cells the mitochondrial metabolism is deregulated. Impaired apoptosis, insensitivity to antigrowth signals and unlimited proliferation have been linked to mitochondrial dysfunction. It is therefore not surprising that mitochondria have emerged as a major target for cancer therapy. Mitochondria-targeting agents are able to bypass resistance mechanisms and to (re-) activate cell-death programs. Methods: Web-based literature searching tools such as SciFinder were used to search for reports on cytotoxic metal complexes that are taken up by the mitochondria and interact with mitochondrial DNA or mitochondrial proteins, disrupt the mitochondrial membrane potential, facilitate mitochondrial membrane permeabilization or activate mitochondria-dependent celldeath signaling by unbalancing the cellular redox state. Included in the search were publications investigating strategies to selectively accumulate metallodrugs in the mitochondria. Results: This review includes 241 references on antimitochondrial metal complexes, the use of mitochondria-targeting carrier ligands and the formation of lipophilic cationic complexes. Conclusion: Recent developments in the design, cytotoxic potency, and mechanistic understanding of antimitochondrial metal complexes, in particular of cyclometalated Au, Ru, Ir and Pt complexes, Ru polypyridine complexes and Au-N-heterocyclic carbene and phosphine complexes are summarized and discussed.

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Ali, Imran, Waseem A. Wani, Kishwar Saleem, and Ming-Fa Hsieh. "Anticancer metallodrugs of glutamic acid sulphonamides: in silico, DNA binding, hemolysis and anticancer studies." RSC Adv. 4, no. 56 (2014): 29629–41. http://dx.doi.org/10.1039/c4ra02570a.

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In response to an increased demand for effective anticancer drugs, a series of disodium sulphonamides ofl-glutamic acid (L1–L3) was synthesized. Sulphonamides were complexed with copper(ii), nickel(ii) and ruthenium(iii) ions, separately and respectively.

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Sun, Wen, Xiaolong Zeng, and Si Wu. "Photoresponsive ruthenium-containing polymers: potential polymeric metallodrugs for anticancer phototherapy." Dalton Transactions 47, no. 2 (2018): 283–86. http://dx.doi.org/10.1039/c7dt03390g.

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Contel, María. "Unconventional Anticancer Metallodrugs and Strategies to Improve Their Pharmacological Profile." Inorganics 7, no. 7 (July 10, 2019): 88. http://dx.doi.org/10.3390/inorganics7070088.

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Zaki, Mehvash, Suboot Hairat, and Elham S. Aazam. "Scope of organometallic compounds based on transition metal-arene systems as anticancer agents: starting from the classical paradigm to targeting multiple strategies." RSC Advances 9, no. 6 (2019): 3239–78. http://dx.doi.org/10.1039/c8ra07926a.

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Abás, Elisa, Diego Aguirre-Ramírez, Mariano Laguna, and Laura Grasa. "Selective Anticancer and Antimicrobial Metallodrugs Based on Gold(III) Dithiocarbamate Complexes." Biomedicines 9, no. 12 (November 26, 2021): 1775. http://dx.doi.org/10.3390/biomedicines9121775.

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New dithiocarbamate cycloaurated complexes have been synthesized and their physicochemical and in vitro antitumor properties have been evaluated. All the performed studies highlighted good transport through the blood and biodistribution, according to the balance between the properties of hydrophilicity/lipophilicity and the binding of moderate strength to the BSA protein. Furthermore, none of the complexes exhibited reduction or decomposition reactions, presenting excellent physiological stability. The in vitro cytotoxic effect was evaluated on human colon cancer cell line Caco-2/TC7, and the complexes showed great antiproliferative activity and excellent selectivity, as much less effect was detected on normal Caco-2/TC7 cells. Most of the complexes exhibit antiproliferative activity that was better than or similar to auranofin, and at least nine times better than that of cisplatin. Its action mechanism is still under discussion since no evidence of cell cycle arrest was found, but an antioxidant role was shown for some of the selective complexes. All complexes were also tested as antimicrobial drugs, exhibiting good activity towards S. aureus and E. coli. bacteria and C. albicans and C. neoformans fungi.

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Arshad, Jahanzaib, Kelvin K. H. Tong, Sanam Movassaghi, Tilo Söhnel, Stephen M. F. Jamieson, Muhammad Hanif, and Christian G. Hartinger. "Impact of the Metal Center and Leaving Group on the Anticancer Activity of Organometallic Complexes of Pyridine-2-carbothioamide." Molecules 26, no. 4 (February 5, 2021): 833. http://dx.doi.org/10.3390/molecules26040833.

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RuII(cym)Cl (cym = η6-p-cymene) complexes of pyridinecarbothioamides have shown potential for development as orally active anticancer metallodrugs, underlined by their high selectivity towards plectin as the molecular target. In order to investigate the impact of the metal center on the anticancer activity and their physicochemical properties, the Os(cym), Rh- and Ir(Cp*) (Cp* = pentamethylcyclopentadienyl) analogues of the most promising and orally active compound plecstatin 2 were prepared and characterized by spectroscopic techniques and X-ray diffraction analysis. Dissolution in aqueous medium results in quick ligand exchange reactions; however, over time no further changes in the 1H NMR spectra were observed. The Rh- and Ir(Cp*) complexes were investigated for their reactions with amino acids, and while they reacted with Cys, no reaction with His was observed. Studies on the in vitro anticancer activity identified the Ru derivatives as the most potent, independent of their halido leaving group, while the Rh derivative was more active than the Ir analogue. This demonstrates that the metal center has a significant impact on the anticancer activity of the compound class.

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Tolbatov, Iogann, Alessandro Marrone, Cecilia Coletti, and Nazzareno Re. "Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey." Molecules 26, no. 24 (December 15, 2021): 7600. http://dx.doi.org/10.3390/molecules26247600.

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Owing to the growing hardware capabilities and the enhancing efficacy of computational methodologies, computational chemistry approaches have constantly become more important in the development of novel anticancer metallodrugs. Besides traditional Pt-based drugs, inorganic and organometallic complexes of other transition metals are showing increasing potential in the treatment of cancer. Among them, Au(I)- and Au(III)-based compounds are promising candidates due to the strong affinity of Au(I) cations to cysteine and selenocysteine side chains of the protein residues and to Au(III) complexes being more labile and prone to the reduction to either Au(I) or Au(0) in the physiological milieu. A correct prediction of metal complexes’ properties and of their bonding interactions with potential ligands requires QM computations, usually at the ab initio or DFT level. However, MM, MD, and docking approaches can also give useful information on their binding site on large biomolecular targets, such as proteins or DNA, provided a careful parametrization of the metal force field is employed. In this review, we provide an overview of the recent computational studies of Au(I) and Au(III) antitumor compounds and of their interactions with biomolecular targets, such as sulfur- and selenium-containing enzymes, like glutathione reductases, glutathione peroxidase, glutathione-S-transferase, cysteine protease, thioredoxin reductase and poly (ADP-ribose) polymerase 1.

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Barry, Nicolas P. E., and Peter J. Sadler. "100 years of metal coordination chemistry: from Alfred Werner to anticancer metallodrugs." Pure and Applied Chemistry 86, no. 12 (December 1, 2014): 1897–910. http://dx.doi.org/10.1515/pac-2014-0504.

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Abstract Alfred Werner was awarded the Nobel Prize in Chemistry just over 100 years ago. We recall briefly the era in which he was working, his co-workers, and the equipment he used in his laboratories. His ideas were ground breaking: not only does a metal ion have a primary valency (“hauptvalenz”, now the oxidation state), but also a secondary valency, the coordination number (“nebenvalenz”). At that time some refused to accept this idea, but he realised that his new thinking would open up new areas of research. Indeed it did. We illustrate this for the emerging field of medicinal metal coordination chemistry, the design of metal-based therapeutic and diagnostic agents. The biological activity of metal complexes depends intimately not only on the metal and its oxidation state, but also on the type and number of coordinated ligands, and the coordination geometry. This provides a rich platform in pharmacological space for structural and electronic diversity. It is necessary to control both the thermodynamics (strengths of metal-ligand bonds) and kinetics of ligand substitution reactions to provide complexes with defined mechanisms of action. Outer-sphere interactions can also play a major role in target recognition. Our current interest is focussed especially on relatively inert metal complexes which were very familiar to Werner (RuII, OsII, RhIII, IrIII, PtII, PtIV).

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Cisnetti, Federico, and Arnaud Gautier. "Metal/N-Heterocyclic Carbene Complexes: Opportunities for the Development of Anticancer Metallodrugs." Angewandte Chemie International Edition 52, no. 46 (October 2, 2013): 11976–78. http://dx.doi.org/10.1002/anie.201306682.

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Zhang, Ya, Xiangchun Zhang, Qing Yuan, Wenchao Niu, Chunyu Zhang, Jiaojiao Li, Zhesheng He, et al. "Peptide-Templated Gold Clusters as Enzyme-Like Catalyst Boost Intracellular Oxidative Pressure and Induce Tumor-Specific Cell Apoptosis." Nanomaterials 8, no. 12 (December 12, 2018): 1040. http://dx.doi.org/10.3390/nano8121040.

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Anticancer metallodrugs that aim to physiological characters unique to tumor microenvironment are expected to combat drug tolerance and side-effects. Recently, owing to the fact that reactive oxygen species’ is closely related to the development of tumors, people are committed to developing metallodrugs with the capacity of improving the level of reactive oxygen species level toinduce oxidative stress in cancer cells. Herein, we demonstrated that peptide templated gold clusters with atomic precision preferably catalyze the transformation of hydrogen peroxide into superoxide anion in oxidative pressure-type tumor cells. Firstly, we successfully constructed gold clusters by rationally designing peptide sequences which targets integrin ανβ3 overexpressed on glioblastoma cells. The superoxide anion, radical derived from hydrogen peroxide and catalyzed by gold clusters, was confirmed in vitro under pseudo-physiological conditions. Then, kinetic parameters were evaluated to verify the catalytic properties of gold clusters. Furthermore, these peptide decorated clusters can serve as special enzyme-like catalyst to convert endogenous hydrogen peroxide into superoxide anion, elevated intracellular reactive oxygen species levels, lower mitochondrial membrane potential, damage biomacromolecules, and trigger tumor cell apoptosis consequently.

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