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Journal articles on the topic 'Antitumor Metallodrugs'

Author: Grafiati
Published: 4 June 2021
Last updated: 6 September 2023

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1

Li, Xuezhao, Zhuolin Shi, Jinguo Wu, Jinlong Wu, Cheng He, Xiaorou Hao, and Chunying Duan. "Lighting up metallohelices: from DNA binders to chemotherapy and photodynamic therapy." Chemical Communications 56, no. 55 (2020): 7537–48. http://dx.doi.org/10.1039/d0cc02194f.

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DNA distortion induced by metallodrugs is one of the main subjects for drug design. In this Feature Article, the developments of DNA-targeted metallohelices for antitumor chemotherapy and photodynamic therapy are presented with future perspectives.
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2

Liu, Wukun, and Ronald Gust. "Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs." Chem. Soc. Rev. 42, no. 2 (2013): 755–73. http://dx.doi.org/10.1039/c2cs35314h.

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3

Liu, Wukun, and Ronald Gust. "ChemInform Abstract: Metal N-Heterocyclic Carbene Complexes as Potential Antitumor Metallodrugs." ChemInform 44, no. 20 (April 25, 2013): no. http://dx.doi.org/10.1002/chin.201320229.

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4

Morais, Tânia S., Andreia Valente, Ana Isabel Tomaz, Fernanda Marques, and Maria Helena Garcia. "Tracking antitumor metallodrugs: promising agents with the Ru(II)- and Fe(II)-cyclopentadienyl scaffolds." Future Medicinal Chemistry 8, no. 5 (April 2016): 527–44. http://dx.doi.org/10.4155/fmc.16.7.

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5

Timerbaev, Andrei R., Christian G. Hartinger, Svetlana S. Aleksenko, and Bernhard K. Keppler. "Interactions of Antitumor Metallodrugs with Serum Proteins: Advances in Characterization Using Modern Analytical Methodology." Chemical Reviews 106, no. 6 (June 2006): 2224–48. http://dx.doi.org/10.1021/cr040704h.

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6

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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7

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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8

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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9

Drius, Giacomo, Silvia Bordoni, Carla Boga, Magda Monari, Jessica Fiori, Erika Esposito, Chiara Zalambani, et al. "Synthesis and Antiproliferative Insights of Lipophilic Ru(II)-Hydroxy Stearic Acid Hybrid Species." Molecules 28, no. 10 (May 12, 2023): 4051. http://dx.doi.org/10.3390/molecules28104051.

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Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H)2CO(PPh3)3] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29.
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10

Petanidis, Savvas, Efrosini Kioseoglou, and Athanasios Salifoglou. "Metallodrugs in Targeted Cancer Therapeutics: Aiming at Chemoresistance- related Patterns and Immunosuppressive Tumor Networks." Current Medicinal Chemistry 26, no. 4 (April 1, 2019): 607–23. http://dx.doi.org/10.2174/0929867324666171116125908.

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Tumor cell chemoresistance is a major challenge in cancer therapeutics. Major select metal-based drugs are potent anticancer mediators yet they exhibit adverse sideeffects and are efficient against limited types of malignancies. A need, therefore, arises for novel metallodrugs with improved efficacy and decreased toxicity. Enhancement of antitumor drugs based on anticancer metals is currently a very active research field, with considerable efforts having been made toward elucidating the mechanisms of immune action of complex metalloforms and optimizing their immunoregulatory bioactivity through appropriate synthetic structural modification(s) and encapsulation in suitable nanocarriers, thereby enhancing their selectivity, specificity, stability, and bioactivity. In that respect, comprehending the molecular factors involved in drug resistance and immune response may help us develop new approaches toward more promising chemotherapies, reducing the rate of relapse and overcoming chemoresistance. In this review, a) molecular immunerelated mechanisms in the tumor microenvironment, responsible for lower drug sensitivity and tumor relapse, along with b) strategies for reversing drug resistance and targeting immunosuppressive tumor networks, while concurrently optimizing the design of complex metalloforms bearing anti-tumor activity, are discussed in an effort to identify and overcome chemoresistance mechanisms for effective tumor immunotherapeutic approaches.
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11

Tolbatov, Iogann, and Alessandro Marrone. "Selenocysteine of thioredoxin reductase as the primary target for the antitumor metallodrugs: A computational point of view." Journal of Organometallic Chemistry 965-966 (May 2022): 122330. http://dx.doi.org/10.1016/j.jorganchem.2022.122330.

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12

Casini, Angela, Chiara Gabbiani, Francesca Sorrentino, Maria Pia Rigobello, Alberto Bindoli, Tilmann J. Geldbach, Alessandro Marrone, et al. "Emerging Protein Targets for Anticancer Metallodrugs: Inhibition of Thioredoxin Reductase and Cathepsin B by Antitumor Ruthenium(II)−Arene Compounds." Journal of Medicinal Chemistry 51, no. 21 (November 13, 2008): 6773–81. http://dx.doi.org/10.1021/jm8006678.

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13

Mármol, Inés, Nerea Jiménez-Moreno, Carmen Ancín-Azpilicueta, Jesús Osada, Elena Cerrada, and María Jesús Rodríguez-Yoldi. "A Combination of Rosa Canina Extracts and Gold Complex Favors Apoptosis of Caco-2 Cells by Increasing Oxidative Stress and Mitochondrial Dysfunction." Antioxidants 9, no. 1 (December 24, 2019): 17. http://dx.doi.org/10.3390/antiox9010017.

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Given the alarming increase in colorectal cancer (CRC) worldwide, novel therapies are urgently needed. Plant-derived extracts have gained considerable interest in the last years due to their strong anticancer effect mediated by their unique bioactive compounds. Specifically, rosehips from Rosa canina have been successfully tested against several cancer models, including colon cancer. Moreover, gold derivatives are a promising alternative to the current platinum-based drugs commonly used in CRC chemotherapy due to their lack of affinity for DNA. Herein we have investigated the antitumor potential of a drug combination made of acidic polyphenols extracted from R. canina and the gold complex (Au(C≡C-2-NC5H4) (PTA)) in Caco-2 cell line as a model of CRC. The combination triggered strong apoptosis mediated by a blockage of the autophagic flux, which might be a consequence of a reactive oxygen species (ROS) increase and mitochondrial dysfunctionality. Our results suggest that the clinical application of plant polyphenols might enhance the anticancer effect of metallodrugs and reduce drug exposure time and therefore its side effects.
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14

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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15

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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16

Espósito, Breno Pannia, and Renato Najjar. "Interactions of antitumoral platinum-group metallodrugs with albumin." Coordination Chemistry Reviews 232, no. 1-2 (October 2002): 137–49. http://dx.doi.org/10.1016/s0010-8545(02)00049-8.

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17

Pereira, Eufrásia S., Gabriel L. S. Rodrigues, and Willian R. Rocha. "Electronic structure and mechanism for the uptake of nitric oxide by the Ru(iii) antitumor complex NAMI-A." RSC Advances 11, no. 13 (2021): 7381–90. http://dx.doi.org/10.1039/d0ra10622d.

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18

Ravera, Mauro, Graziana Bagni, Marco Mascini, and Domenico Osella. "DNA-Metallodrugs Interactions Signaled by Electrochemical Biosensors: An Overview." Bioinorganic Chemistry and Applications 2007 (2007): 1–11. http://dx.doi.org/10.1155/2007/91078.

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The interaction of drugs with DNA is an important aspect in pharmacology. In recent years, many important technological advances have been made to develop new techniques to monitor biorecognition and biointeraction on solid devices. The interaction between DNA and drugs can cause chemical and conformational modifications and, thus, variation of the electrochemical properties of nucleobases. The propensity of a given compound to interact with DNA is measured as a function of the decrease of guanine oxidation signal on a DNA electrochemical biosensor. Covalent binding at N7 of guanine, electrostatic interactions, and intercalation are the events that this kind of biosensor can detect. In this context, the interaction between a panel of antitumoral Pt-, Ru-, and Ti-based metallodrugs with DNA immobilized on screen-printed electrodes has been studied. The DNA biosensors are used for semiquantitative evaluation of the analogous interaction occurring in the biological environment.
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19

Balsa, Lucia M., María R. Rodriguez, Verónica Ferraresi-Curotto, Beatriz S. Parajón-Costa, Ana C. Gonzalez-Baró, and Ignacio E. León. "Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics." International Journal of Molecular Sciences 24, no. 8 (April 19, 2023): 7531. http://dx.doi.org/10.3390/ijms24087531.

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Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to the usually employed platinum-derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazone complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in endoplasmic reticulum stress and unfolded protein response, as well as the downregulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of gain-of-function-mutant p53. Moreover, we found a novel and interesting effect for a copper metallodrug, which was the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels.
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Ravera, Mauro, Elisabetta Gabano, Ilaria Zanellato, Elena Perin, Aldo Arrais, and Domenico Osella. "Polyanionic Biopolymers for the Delivery of Pt(II) Cationic Antiproliferative Complexes." Bioinorganic Chemistry and Applications 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/2380540.

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Phenanthriplatin, that is, (SP-4-3)-diamminechlorido(phenanthridine)platinum(II) nitrate, an effective antitumor cationic Pt(II) complex, was loaded on negatively charged dextran sulfate (DS) as a model vector for drug deliveryviaelectrostatic interactions. The free complex and the corresponding conjugate withDSwere tested on two standard human tumor cell lines, namely, ovarian A2780 and colon HCT 116, and on several malignant pleural mesothelioma cell lines (namely, epithelioid BR95, mixed/biphasic MG06, sarcomatoid MM98, and sarcomatoid cisplatin-resistant MM98R). Thein vitroresults suggest that the conjugate releases the active metabolite phenanthriplatin with a biphasic fashion. In these experimental conditions, the conjugate is slightly less active than free phenanthriplatin; but both exhibited antiproliferative potency higher than the reference metallodrug cisplatin and were able to overcome the acquired cisplatin chemoresistance in MM98R cells.
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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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22

Bondžić, Aleksandra M., Andreja R. Leskovac, Sandra Ž. Petrović, Dragana D. Vasić Anićijević, Marco Luce, Lara Massai, Amanda Generosi, et al. "Conjugates of Gold Nanoparticles and Antitumor Gold(III) Complexes as a Tool for Their AFM and SERS Detection in Biological Tissue." International Journal of Molecular Sciences 20, no. 24 (December 13, 2019): 6306. http://dx.doi.org/10.3390/ijms20246306.

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Citrate-capped gold nanoparticles (AuNPs) were functionalized with three distinct antitumor gold(III) complexes, e.g., [Au(N,N)(OH)2][PF6], where (N,N)=2,2′-bipyridine; [Au(C,N)(AcO)2], where (C,N)=deprotonated 6-(1,1-dimethylbenzyl)-pyridine; [Au(C,N,N)(OH)][PF6], where (C,N,N)=deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine, to assess the chance of tracking their subcellular distribution by atomic force microscopy (AFM), and surface enhanced Raman spectroscopy (SERS) techniques. An extensive physicochemical characterization of the formed conjugates was, thus, carried out by applying a variety of methods (density functional theory—DFT, UV/Vis spectrophotometry, AFM, Raman spectroscopy, and SERS). The resulting gold(III) complexes/AuNPs conjugates turned out to be pretty stable. Interestingly, they exhibited a dramatically increased resonance intensity in the Raman spectra induced by AuNPs. For testing the use of the functionalized AuNPs for biosensing, their distribution in the nuclear, cytosolic, and membrane cell fractions obtained from human lymphocytes was investigated by AFM and SERS. The conjugates were detected in the membrane and nuclear cell fractions but not in the cytosol. The AFM method confirmed that conjugates induced changes in the morphology and nanostructure of the membrane and nuclear fractions. The obtained results point out that the conjugates formed between AuNPs and gold(III) complexes may be used as a tool for tracking metallodrug distribution in the different cell fractions.
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23

Polec-Pawlak, Kasia, Jan K. Abramski, Olga Semenova, Christian G. Hartinger, Andrei R. Timerbaev, Bernhard K. Keppler, and Maciej Jarosz. "Platinum group metallodrug-protein binding studies by capillary electrophoresis – inductively coupled plasma-mass spectrometry: A further insight into the reactivity of a novel antitumor ruthenium(III) complex toward human serum proteins." ELECTROPHORESIS 27, no. 5-6 (March 2006): 1128–35. http://dx.doi.org/10.1002/elps.200500694.

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24

Xue, Xuling, Chenggen Qian, Qin Tao, Yuanxin Dai, Mengdi Lv, Jingwen Dong, Zhi Su, et al. "Using bioorthogonally catalyzed lethality strategy to generate mitochondria-targeting antitumor metallodrugs in vitro and in vivo." National Science Review, November 25, 2020. http://dx.doi.org/10.1093/nsr/nwaa286.

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Abstract Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anticancer therapies. To exploit the synthetic lethality concept in the design of chemical anticancer agents, we developed a bioorthogonally catalyzed lethality (BCL) strategy to generate targeting antitumor metallodrugs both in vitro and in vivo. Metallodrug Ru-rhein was generated from two nontoxic species Ru-N3 and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The nontoxic species Ru-arene complex Ru-N3 and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (> 83%) and showed high antitumor efficacy in vitro. This BCL strategy achieved a remarkable tumor suppression effect on the tumor-bearing mice models. It is interesting that the combination of metal-arene complexes with rhein via CuAAC reaction could transform two nontoxic species into a targeting anticancer metallodrug both in vitro and in vivo, while the product Ru-rhein was nontoxic towards normal cells. This is the first example that exclusive endogenous copper was used to generate metal-based anticancer drugs for cancer treatment. The anticancer mechanism of Ru-rhein was studied and autophagy was induced by increased reactive oxygen species and mitochondrial damage. The generality of this BCL strategy was also studied and it could be extended to other metal complexes such as Os-arene and Ir-arene complexes. Compared with the traditional methods for cancer treatment, this work presented a new approach to generate targeting metallodrugs in vivo via the BCL strategy from nontoxic species in the metal-based chemotherapy.
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Xu, Xianzhi, Feng Dai, Yiting Mao, Kai Zhang, Ying Qin, and Jiwei Zheng. "Metallodrugs in the battle against non-small cell lung cancer: unlocking the potential for improved therapeutic outcomes." Frontiers in Pharmacology 14 (August 31, 2023). http://dx.doi.org/10.3389/fphar.2023.1242488.

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Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Platinum-based chemotherapy is standard-of-care but has limitations including toxicity and resistance. Metal complexes of gold, ruthenium, and other metals have emerged as promising alternatives. This review provides a comprehensive analysis of metallodrugs for NSCLC. Bibliometric analysis reveals growing interest in elucidating mechanisms, developing targeted therapies, and synergistic combinations. Classification of metallodrugs highlights platinum, gold, and ruthenium compounds, as well as emerging metals. Diverse mechanisms include DNA damage, redox modulation, and immunomodulation. Preclinical studies demonstrate cytotoxicity and antitumor effects in vitro and in vivo, providing proof-of-concept. Clinical trials indicate platinums have utility but resistance remains problematic. Non-platinum metallodrugs exhibit favorable safety but modest single agent efficacy to date. Drug delivery approaches like nanoparticles show potential to enhance therapeutic index. Future directions include optimization of metal-based complexes, elucidation of resistance mechanisms, biomarker development, and combination therapies to fully realize the promise of metallodrugs for NSCLC.
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Syed Annuar, Sharifah Nadhira, Nurul Farahana Kamaludin, Normah Awang, and Kok Meng Chan. "Cellular Basis of Organotin(IV) Derivatives as Anticancer Metallodrugs: A Review." Frontiers in Chemistry 9 (July 23, 2021). http://dx.doi.org/10.3389/fchem.2021.657599.

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Organotin(IV) compounds have wide applications in industrial and agricultural fields owing to their ability to act as poly(vinyl chloride) stabilizers and catalytic agents as well as their medicinal properties. Moreover, organotin(IV) compounds may have applications as antitumor, anti-inflammatory, antifungal, or antimicrobial agents based on the observation of synergistic effects following the binding of their respective ligands, resulting in the enhancement of their biological activities. In this review, we describe the antiproliferative activities of organotin(IV) compounds in various human cancer cell lines based on different types of ligands. We also discuss the molecular mechanisms through which organotin(IV) compounds induce cell death via apoptosis through the mitochondrial intrinsic pathway. Finally, we present the mechanisms of cell cycle arrest induced by organotin(IV) compounds. Our report provides a basis for studies of the antitumor activities of organotin(IV) compounds and highlights the potential applications of these compounds as anticancer metallodrugs with low toxicity and few side effects.
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Ma, Jing, Ruijuan Ma, Xueke Zeng, Liming Zhang, Jianing Liu, Wei Zhang, Tao Li, et al. "Lysosome blockade induces divergent metabolic programs in macrophages and tumours for cancer immunotherapy." Journal of Experimental & Clinical Cancer Research 42, no. 1 (August 4, 2023). http://dx.doi.org/10.1186/s13046-023-02768-0.

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Abstract Background Platinum-drugs based chemotherapy in clinic increases the potency of tumor cells to produce M2 macrophages, thus leading to poor anti-metastatic activity and immunosuppression. Lysosome metabolism is critical for cancer cell migration and invasion, but how it promotes antitumor immunity in tumours and macrophages is poorly understood and the underlying mechanisms are elusive. The present study aimed to explore a synergistic strategy to dismantle the immunosuppressive microenvironment of tumours and metallodrugs discovery by using the herent metabolic plasticity. Methods Naphplatin was prepared by coordinating an active alkaline moiety to cisplatin, which can regulate the lysosomal functions. Colorectal carcinoma cells were selected to perform the in vivo biological assays. Blood, tumour and spleen tissues were collected and analyzed by flow cytometry to further explore the relationship between anti-tumour activity and immune cells. Transformations of bone marrow derived macrophage (BMDM) and M2-BMDM to the M1 phenotype was confirmed after treatment with naphplatin. The key mechanisms of lysosome-mediated mucolipin-1(Mcoln1) and mitogen-activated protein kinase (MAPK) activation in M2 macrophage polarization have been unveiled. RNA sequencing (RNA-seq) was used to further explore the key mechanism underlying high-mobility group box 1(HMGB1)-mediated Cathepsin L(CTSL)-lysosome function blockade. Results We demonstrated that naphplatin induces divergent lysosomal metabolic programs and reprograms macrophages in tumor cells to terminate the vicious tumour-associated macrophages (TAMs)-MDSCs-Treg triangle. Mechanistically, macrophages treated with naphplatin cause lysosome metabolic activation by triggering Ca2+ release via Mcoln1, which induces the activation of p38 and nuclear factor-κB (NF-κB) and finally results in polarizing M2 macrophages. In contrast, HMGB1-mediated lysosome metabolic blockade in cancer cells is strongly linked to antitumor effects by promoting cytoplasmic translocation of HMGB1. Conclusions This study reveals the crucial strategies of macrophage-based metallodrugs discovery that are able to treat both immunologically “hot” and “cold” cancers. Different from traditional platinum-based antitumour drugs by inhibition of DNAs, we also deliver a strong antitumour strategy by targeting lysosome to induce divergent metabolic programs in macrophages and tumours for cancer immunotherapy.
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28

Timerbaev, Andrei R., Christian G. Hartinger, Svetlana S. Aleksenko, and Bernhard K. Keppler. "Interactions of Antitumor Metallodrugs with Serum Proteins: Advances in Characterization Using Modern Analytical Methodology." ChemInform 37, no. 37 (September 12, 2006). http://dx.doi.org/10.1002/chin.200637264.

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29

"MN4-based G4-Ligands as Potential Antitumor Agents: A Review." Biointerface Research in Applied Chemistry 12, no. 3 (August 13, 2021): 3977–88. http://dx.doi.org/10.33263/briac123.39773988.

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Cisplatin-based metal drugs have been widely used clinically as anticancer agents. However, these drugs also harm ordinary tissues because cisplatin kills cancer cells by attacking genomic DNA. Therefore, it has been shown that cisplatin-based metal drugs have some serious side effects that cannot be avoided. In order to replace the target site of genomic DNA, G-quadruplex nucleic acid is considered to be an alternative and attractive target for anticancer agents because G-quadruplex always folds into a parallel topology and is, therefore, more important than DNA. This review discussed the recent advancements in the rational design and the development of metal complexes containing anticancer drugs to interact and stabilize or cleave the G4 structure selectively. Further, we also highlighted the G4-interacting transition metal complexes, interacting modes, and their potentials to serve as anticancer drugs in the medical field. The significance of this survey lies in designing the metallodrugs from the most fundamental characteristic of electronic structural engineering to an increasingly reasonable dimension of bio-science.
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30

Ortega-Forte, Enrique, Samanta Hernández-García, Gloria Vigueras, Paula Henarejos-Escudero, Natalia Cutillas, José Ruiz, and Fernando Gandía-Herrero. "Potent anticancer activity of a novel iridium metallodrug via oncosis." Cellular and Molecular Life Sciences 79, no. 10 (September 6, 2022). http://dx.doi.org/10.1007/s00018-022-04526-5.

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AbstractOncosis (from Greek ónkos, meaning “swelling”) is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of cell death induced by anticancer drugs, oncosis has been relatively less explored but holds potential to overcome drug resistance phenomena. In this study, we report a novel rationally designed mitochondria-targeted iridium(III) complex (OncoIr3) with advantageous properties as a bioimaging agent. OncoIr3 exhibited potent anticancer activity in vitro against cancer cells and displayed low toxicity to normal dividing cells. Flow cytometry and fluorescence-based assays confirmed an apoptosis-independent mechanism involving energy depletion, mitochondrial dysfunction and cellular swelling that matched with the oncotic process. Furthermore, a Caenorhabditis elegans tumoral model was developed to test this compound in vivo, which allowed us to prove a strong oncosis-derived antitumor activity in animals (with a 41% reduction of tumor area). Indeed, OncoIr3 was non-toxic to the nematodes and extended their mean lifespan by 18%. Altogether, these findings might shed new light on the development of anticancer metallodrugs with non-conventional modes of action such as oncosis, which could be of particular interest for the treatment of apoptosis-resistant cancers. Graphical abstract
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31

Dhingra, Naveen, S. Khaturia, Har Lal Singh, and VS Solanki. "Synthesis of New Zirconium(IV) Schiff-base Complexes: Spectral, Theoretical, and Molecular Docking Studies." Current Indian Science 01 (July 21, 2023). http://dx.doi.org/10.2174/2210299x01666230721153433.

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Background: The development of the discipline of coordination chemistry owes a great deal to the use of Schiff-base metal chelates. Both Schiff base ligands and metal complexes are of interest due to their potential pharmacological effects. Schiff base derivatives have an extensive range of biological effects, including antitumor, antifungal, antibacterial, anticonvulsant, and antiviral properties. Objective: This study aimed to study the inorganic compound-based metallodrugs that have recently come into existence to provide an effective mechanism for medications that depend on the metal used and its characteristics. An effective platform for diverse pharmacological and therapeutic uses can be found in medicinal complex substances. Methods: The bi-molar reactions of zirconium tetrachloride with bidentate ligands were carried out in dry THF and were characterized by IR, UV-Visible, NMR and C, H, N, S analysis. The DFT method was used to investigate the molecular stability and bond strengths. Gaussian 09 and MolDock were used to optimise the geometry and to calculate the binding energy of all the complexes, respectively. Results: The analysis of the data revealed that the Schiff base, which has bivalent ligands (NS), was coordinated to zirconium via nitrogen and sulfur atoms. The optimum values for the structural parameters were calculated by density functional theory. Compound 5 showed the highest MolDock Score (-123.47 kcal/ mol) and H-bond interaction with active amino acids. Conclusion: The spectroscopic result indicates that the zirconium compounds were all non-electrolyte monomers with deformed octahedral structures. Compound 5 was shown to be the most active and effective of the bunch by both Gaussian software calculations and molecular docking study.
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32

Raković, Ivana, Jovana Bogojeski, Katarina Mladenović, Angelina Petrović, Vera Divac, Kristina Mihailović, Biljana Popovska Jovicić, et al. "Synthesis, Characterization and Biological Studies of a Organoselenium trans-Palladium(II) Complexes." Medicinal Chemistry 16 (September 30, 2020). http://dx.doi.org/10.2174/1573406416666200930112442.

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Background: Over the years, transition metal complexes have exhibited significant antimicrobial and antitumor activity. It all started with cisplatin discovery, but due to the large number of side effects it shows, there is a growing need to find a new metal-based compound with higher selectivity and activity on more tumors. Objectives: Two novel trans-palladium(II) complexes with organoselenium compounds as ligands, [Pd(L1)2Cl2] (L1 = 5- (phenylselanylmethyl)-dihydrofuran-2(3H)-one) and [Pd(L2)2Cl2] (L2 = 2-methyl-5-(phenylselanylmethyl)- tetrahydrofuran) were synthesized, in the text referred to as Pd-Se1 and Pd-Se2. Also, a structurally similar trans-palladium(II) complex, [Pd(L3)2Cl2] (L3= 2,2-dimethyl-3-(phenylselanylmethyl)-tetrahydro-2H-pyran ) was synthesized according to an already published work and is referred to as Pd-Se3. The interaction of synthesized complexes with DNA and bovine serum albumin were done. Also, antimicrobial activity and in vitro testing, cell viability, and cytotoxic effects of synthesized ligands and complexes on human epithelial colorectal cancer cell line HCT-116 were studied. Molecular docking simulations were performed to understand better the binding modes of the complexes reported in this paper with DNA and BSA, as well as to comprehend their antimicrobial activity. Methods: The interactions of the synthesized complexes with DNA and bovine serum albumin were done using UV-Vis and emission spectral studies as well as docking studies. Antimicrobial activity was tested by determining the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) using the resazurin microdilution plate method. Cytotoxic activity on cancer cells was studied by MTT test. Results: The Pd(II) complexes showed a significant binding affinity for calf thymus DNA and bovine serum albumin by UV-Vis and emission spectral studies. The intensity of antimicrobial activity varied with the complexes Pd-Se1 and Pd-Se3, showing significantly higher activity than the corresponding ligand. The most significant activity was shown on Pseudomo-nas aeruginosa. Under standardized laboratory conditions for in vitro testing, cell viability and cytotoxic effects of synthesized ligands and complexes were studied on human epithelial colorectal cancer cell line HCT-116, where Pd-Se2 showed some significant cytotoxic effects. Conclusion: The newly synthesized complexes have the potential to be further investigated as metallodrugs.
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G. Arzoumanidis, Gregory. "New Antitumor Organotitanium Complexes with a Pendant Biologically Active Diazo Group." Fine Chemical Engineering, September 22, 2022, P171—P181. http://dx.doi.org/10.37256/fce.3220221820.

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The ligand of antitumor organotitanium or other metallodrug complexes plays a pivotal role in determining the mechanism of their cytotoxic action. Although the specific contribution of several ligands is generally well established, our understanding of the overall mechanism of the cytotoxic action of the complexes themselves is limited and incomplete in most cases, except perhaps in the case of cis-platin. A strategy to monitor the mode of cytotoxic action of candidate antitumor complexes requires tagging with bioactive side chains like a diazo group, for in-cell site-specific labelling. In this review we discuss new methods for the preparation of potential antitumor organotitanium complexes with a pendant diazo group, aiming at better understanding their mode of cytotoxic action. By introducing this new class of titanium-based potential antitumor agents, we hope to contribute to the world-wide effort in this important area of medicinal chemistry research, for an ultimate usable titanium-based antitumor drug. The following figure represents a model reaction depicting the methodology, for the formation of a bioactive Titanium complex with a pendant diazo group. Moreover, in this case, a scheme is required that represents all the possibilities of formation of the bioactive complex of titanium with a pendant diazo group.
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34

Gómez-Ruiz, Santiago, Sanjiv Prashar, Álvar Serrano-Pindado, Michael Aondona Iorhemba, Diana Díaz-García, Miguel Díaz-Sánchez, and Irene Mena-Palomo. "Cytotoxic and DNA-binding capacity of titanocene functionalized mesoporous nanoparticles in breast cancer cell lines MCF-7 and MDA-MB-231." Current Pharmaceutical Design 29 (July 27, 2023). http://dx.doi.org/10.2174/1381612829666230727115356.

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Aims: The fight against cancer is an active research topic that combines several disciplines to find suitable agents to treat various tumours. Background: Following cisplatin, organometallic compounds, including titanocene derivatives, have been tested as antitumoral agents. However, key issues still need to be addressed in metallodrug chemotherapy relating to solubility, stability, and dosage. Mesoporous silica nanoparticles, being low toxic biocompatible materials with high loading capacity, are ideal candidates to overcome these problems. Objective: This study aimed to prepare and structurally characterize titanocene functionalized mesoporous silica nanoparticles and evaluate their cytotoxic activity against cancer cells. Methods: The preparation of titanocene functionalized mesoporous silica nanoparticles was achieved by synthetic protocols, involving either grafting or tethering. Characterization was carried out using standard techniques, FT-IR, XRD, XRF, TEM, and BET. The titanocene functionalized materials were studied as antitumoral agents in the breast cancer lines MCF-7 and MDA-MB-231. Results: Results: The functionalized MSN showed promising antitumoral activity against cells lines MCF-7 and MDA-MB-231 up to 9 times more than titanocene alone. Conclusion: This study reported the potential of titanocene-functionalized mesoporous silica nanoparticles in future chemotherapeutic actions.
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