Novel Metal-Based Drugs for Anticancer and Antiviral Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 34558

Special Issue Editors


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Department of Biological and Environmental Sciences and Technologies, University of Salento, Piazza Tancredi, 7, 73100 Lecce, LE, Italy
Interests: metal-based drugs; synthesis; bioinorganic chemistry; anticancer drugs; NMR-based metabolomics; coordination chemistry

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Guest Editor
Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, 56124 Pisa, Italy
Interests: bioinorganic chemistry; inorganic chemistry; NMR; metal-based drugs; chemotherapeutic agents
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Special Issue Information

Dear Colleagues,

The discovery of the antiproliferative properties of cisplatin and its subsequent use in cancer treatment has attracted great interest in the family of transition metal complexes. For this reason, researchers have focused their attention on the development of new metal-based drugs as possible candidates for clinical use. These efforts have been mostly devoted to expanding the clinical application of this family of compounds as well as to overcoming the main problems related to cisplatin administration in cancer treatment (such as the development of resistance and its severe side effects).

The coordination numbers and geometries, the different available redox states, and the various kinetic properties of transition metal complexes result in a variety of opportunities in the design of new metal-based drugs.

Moreover, the broad potential of transition metal complexes has attracted great interest from researchers, originating new points of view and new perspectives for their use in a large range of applications, also beyond the original anticancer purposes.

Against this backdrop, this Special Issue aims to collect research articles, comprehensive reviews, and short communications focused on the design, synthesis, and preclinical or clinical evidence of novel metal-based drugs for anticancer and antiviral applications.

Dr. Federica De Castro
Dr. Damiano Cirri
Guest Editors

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Keywords

  • metal complexes
  • antitumor
  • antiviral
  • coordination compounds
  • metal-based drugs

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Published Papers (12 papers)

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Research

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17 pages, 1680 KiB  
Article
Pyrenebutyrate Pt(IV) Complexes with Nanomolar Anticancer Activity
by Anife Ahmedova, Rositsa Mihaylova, Silviya Stoykova, Veronika Mihaylova, Nikola Burdzhiev, Viktoria Elincheva, Georgi Momekov and Denitsa Momekova
Pharmaceutics 2023, 15(9), 2310; https://doi.org/10.3390/pharmaceutics15092310 - 13 Sep 2023
Cited by 2 | Viewed by 1455
Abstract
Research on platinum-based anticancer drugs continuously strives to develop new non-classical platinum complexes. Pt(IV) prodrugs are the most promising, and their activation-by-reduction mechanism of action is being explored as a prospect for higher selectivity and efficiency. Herein, we present the anticancer potency and [...] Read more.
Research on platinum-based anticancer drugs continuously strives to develop new non-classical platinum complexes. Pt(IV) prodrugs are the most promising, and their activation-by-reduction mechanism of action is being explored as a prospect for higher selectivity and efficiency. Herein, we present the anticancer potency and chemical reactivity of Pt(IV) complexes formed by linking pyrene butyric acid with cisplatin. The results from cytotoxicity screening on 10 types of cancer cell lines and non-malignant cells (HEK-293) indicated IC50 values as low as 50–70 nM for the monosubstituted Pt(IV) complex against leukemia cell lines (HL-60 and SKW3) and a cisplatin-resistant derivative (HL-60/CDDP). Interestingly, the bis-substituted complex is virtually non-toxic to both healthy and cancerous cells of adherent types. Nevertheless, it shows high cytotoxicity against multidrug-resistant derivatives HL-60/CDDP and HL-60/Dox. The reactivity of the complexes with biological reductants was monitored by the NMR method. Furthermore, the platinum uptake by the treated cells was examined on two types of cellular cultures: adherent and suspension growing, and proteome profiling was conducted to track expression changes of key apoptosis-related proteins in HL-60 cells. The general conclusion points to a possible cytoskeletal entrapment of the bulkier bis-pyrene complex that could be limiting its cytotoxicity to adherent cells, both cancerous and healthy ones. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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30 pages, 14839 KiB  
Article
One-Step Phytofabrication Method of Silver and Gold Nanoparticles Using Haloxylon salicornicum for Anticancer, Antimicrobial, and Antioxidant Activities
by Reham Samir Hamida, Mohamed Abdelaal Ali, Haifa Essa Alfassam, Maha Abdullah Momenah, Mariam Abdulaziz Alkhateeb and Mashael Mohammed Bin-Meferij
Pharmaceutics 2023, 15(2), 529; https://doi.org/10.3390/pharmaceutics15020529 - 4 Feb 2023
Cited by 8 | Viewed by 2369
Abstract
Among various routes of metallic nanoparticle (NPs) fabrication, phytosynthesis has significant advantages over other conventional approaches. Plant-mediated synthesis of NPs is a fast, one-step, ecobenign, and inexpensive method with high scalability. Herein, silver (Ag) and gold (Au)-NPs were extracellularly synthesized using aqueous Haloxylon [...] Read more.
Among various routes of metallic nanoparticle (NPs) fabrication, phytosynthesis has significant advantages over other conventional approaches. Plant-mediated synthesis of NPs is a fast, one-step, ecobenign, and inexpensive method with high scalability. Herein, silver (Ag) and gold (Au)-NPs were extracellularly synthesized using aqueous Haloxylon salicornicum (H@Ag-, H@Au-NPs) leaf extracts. GC-MS was performed to analyze the chemical compositions of H. salicornicum extract. H@Ag- and H@Au-NPs were characterized via UV-Vis spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission and scanning electron microscopy, and Zetasizer. H@Ag- and H@Au-NPs have surface plasmon resonance at 435.5 and 530.3 nm, respectively. FTIR and GC-MS data suggest that secondary plant metabolites and hydrocarbons might be responsible for the reduction and stabilization of NPs. XRD demonstrated that both NPs have a crystalline nature. H@Ag-NPs have a uniform spherical shape, whereas H@Au-NPs are spherical with few oval and triangular shapes, and their average nanosizes were 19.1 ± 0.8 and 8.1 ± 0.3 nm, respectively. Hydrodynamic diameters of H@Ag-NPs and H@Au-NPs were 184.7 nm, 56.4, and 295.4 nm, and their potential charges were −24.0 and −24.4 mV, respectively. The inhibitory activity of 500 µg/mL H@Ag- and H@Au-NPs was tested against Sw480, Sw620, HCT-116, and Caco-2 colon cancer cell lines and two normal cell lines, including HFs and Vero. H@Ag-NPs revealed potent anticancer activity against all cancer cells at low concentrations. Sw480 was the most sensitive cell to H@Ag-NPs, whereas Sw620 was the least permeable one. These findings suggested that the antiproliferative activity of H@Ag-NPs is cell-response-dependent and may be influenced by a variety of factors, including the cellular metabolic state, which influences cellular charge and interactions with charged NPs. Although H@Au-NPs were smaller, their reactivity against cancer cells was weak, suggesting that the chemical properties, metal structure, quantity and chemistry of the functional groups on the NP surface may influence their reactivity. The biocidal activity of 1 mg/mL H@Ag- and H@Au-NPs against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Klebsiella pneumoniae was assessed. H@Ag-NPs showed biocidal activity against Gram-positive bacteria compared to Gram-negative bacteria, whereas H@Au-NPs showed no inhibitory activity. FRAP and DPPH assays were used to determine the scavenging activity of the plant extracts and both NPs. H@Ag-NPs (1 mg/mL) had the greatest scavenging activity compared to tested drugs. These findings suggest that H@Ag-NPs are potent anticancer, antibacterial, and antioxidant agents, while H@Au-NPs may be used as a drug vehicle for pharmaceutical applications. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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19 pages, 20935 KiB  
Article
Comparing the Variants of Iron Oxide Nanoparticle-Mediated Delivery of miRNA34a for Efficiency in Silencing of PD-L1 Genes in Cancer Cells
by Richa Pandey, Feng-Shuo Yang, Vyshnav Punnath Sivasankaran, Yu-Lun Lo, Yi-Ting Wu, Chia-Yu Chang, Chien-Chih Chiu, Zi-Xian Liao and Li-Fang Wang
Pharmaceutics 2023, 15(1), 215; https://doi.org/10.3390/pharmaceutics15010215 - 8 Jan 2023
Cited by 7 | Viewed by 3160
Abstract
The blocking of programmed death-ligand 1 (PD-L1) in tumor cells represents a powerful strategy in cancer immunotherapy. Using viral vectors to deliver the cargo for inactivating the PD-L1 gene could be associated with host cell genotoxicity and concomitant immune attack. To develop an [...] Read more.
The blocking of programmed death-ligand 1 (PD-L1) in tumor cells represents a powerful strategy in cancer immunotherapy. Using viral vectors to deliver the cargo for inactivating the PD-L1 gene could be associated with host cell genotoxicity and concomitant immune attack. To develop an alternative safe gene delivery method, we designed a unique combination for miRNA34a delivery using a transgene carrier in the form of iron oxide magnetic nanoparticles (IONPs) via magnetofection to downregulate PD-L1 expression in cancer cells. We synthesized IONPs of multiple shapes (IONRs (iron oxide nanorods), IONSs (iron oxide nanospheres), and ITOHs (iron oxide truncated octahedrons)), surface-functionalized with polyethyleneimine (PEI) using the ligand exchange method, as gene delivery systems. Under the guidance of an external magnetic field, PEI@IONPs loaded with plasmid DNA (DNA/PEI@IONPs) encoding GFP showed high transfection efficiency at different weight ratios and time points in A549 and MDA-MB-231 cells. Additionally, the DNA/PEI@IONPs with miRNA34a inserts under a static magnetic field resulted in significant knockdown of the PD-L1 gene, as demonstrated via immunoblotting of the PD-L1 protein. Among the three shapes of IONPs, IONRs showed the highest PD-L1 knockdown efficiency. The genetic expression of miRNA34a was also studied using qPCR and it showed high expression of miRNA in cells treated with PEI@IONRs. Flow cytometry and a live/dead assay confirmed apoptosis after transfection with miRNA34a. To conclude, in this paper, a promising transgene carrier with low cost, negligible cytotoxicity, and high transfection efficiency has been successfully established for miRNA gene delivery in the context of cancer immunotherapy. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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14 pages, 12342 KiB  
Article
Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Functionalized to EGF and Ce6 Complexes for Breast Cancer Diagnoses and Therapy
by Marcela Cândido, Paula Vieira, Andrea Campos, Cristina Soares and Leandro Raniero
Pharmaceutics 2023, 15(1), 100; https://doi.org/10.3390/pharmaceutics15010100 - 28 Dec 2022
Cited by 6 | Viewed by 2296
Abstract
Superparamagnetic iron oxide nanoparticles (SPIONs) have some limitations in the physiological environment, however, a modification on their surface, such as a core–shell structure with gold (SPIONs@Au), can enhance their applicability. In this study, SPIONs were synthesized by the chemical coprecipitation method, stabilized by [...] Read more.
Superparamagnetic iron oxide nanoparticles (SPIONs) have some limitations in the physiological environment, however, a modification on their surface, such as a core–shell structure with gold (SPIONs@Au), can enhance their applicability. In this study, SPIONs were synthesized by the chemical coprecipitation method, stabilized by sodium citrate, and followed by the gold-coating process. SPIONs@Au were functionalized with EGF-α-lipoic acid and chlorin e6 (Ce6)-cysteamine complexes, composing a Theranostic Nanoprobe (TP). The outcomes showed that the SPIONs@Au had changed in color to red and had an absorption band centered at 530 nm. The coating was verified in the TEM micrographs in bright and dark fields by EDS mapping, which indicated the presence of Au and Fe. The Ce6-cysteamine complex had a resonant band at 670 nm that enabled the diagnosis of biological samples using fluorescence analysis. In the measure of TNBC cell uptake, the maximum value of TP fluorescence intensity was obtained within 4 h of internalization. At 2 h, the incorporation of the TP in the cytoplasm as well as in the nuclei was observed, suggesting that it could be employed as a diagnostic marker. The PTT results showed significant percentages of apoptosis in the TNBC cell line, which confirms the efficacy of the TP. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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22 pages, 4469 KiB  
Article
Arene Variation of Highly Cytotoxic Tridentate Naphthoquinone-Based Ruthenium(II) Complexes and In-Depth In Vitro Studies
by Klaudia Cseh, Heiko Geisler, Kristina Stanojkovska, Julia Westermayr, Philipp Brunmayr, Dominik Wenisch, Natalie Gajic, Michaela Hejl, Martin Schaier, Gunda Koellensperger, Michael A. Jakupec, Philipp Marquetand and Wolfgang Kandioller
Pharmaceutics 2022, 14(11), 2466; https://doi.org/10.3390/pharmaceutics14112466 - 15 Nov 2022
Cited by 9 | Viewed by 2645
Abstract
The main purpose of this study was to synthesize a new set of naphthoquinone-based ruthenium(II) arene complexes and to develop an understanding of their mode of action. This study systematically reviews the steps of synthesis, aiming to provide a simplified approach using microwave [...] Read more.
The main purpose of this study was to synthesize a new set of naphthoquinone-based ruthenium(II) arene complexes and to develop an understanding of their mode of action. This study systematically reviews the steps of synthesis, aiming to provide a simplified approach using microwave irradiation. The chemical structures and the physicochemical properties of this novel group of compounds were examined by 1H-NMR and 13C-NMR spectroscopy, X-ray diffractometry, HPLC-MS and supporting DFT calculations. Several aspects of the biological activity were investigated in vitro, including short- and long-term cytotoxicity tests, cellular accumulation studies, detection of reactive oxygen species generation, apoptosis induction and NAD(P)H:quinone oxidoreductase 1 (NQO1) activity as well as cell cycle analysis in A549, CH1/PA-1, and SW480 cancer cells. Furthermore, the DNA interaction ability was studied in a cell-free assay. A positive correlation was found between cytotoxicity, lipophilicity and cellular accumulation of the tested complexes, and the results offer some important insights into the effects of the arene. The most obvious finding to emerge from this study is that the usually very chemosensitive CH1/PA-1 teratocarcinoma cells showed resistance to these phthiocol-based organometallics in comparison to the usually less chemosensitive SW480 colon carcinoma cells, which pilot experiments suggest as being related to NQO1 activity. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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14 pages, 2504 KiB  
Article
DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes
by Burcu Saygıdeğer Demir, Simay İnce, Mustafa Kemal Yilmaz, Aycan Sezan, Ezgi Derinöz, Tugba Taskin-Tok and Yasemin Saygideger
Pharmaceutics 2022, 14(11), 2409; https://doi.org/10.3390/pharmaceutics14112409 - 8 Nov 2022
Cited by 7 | Viewed by 2002
Abstract
DNA has become the target of metal complexes in cancer drug discovery. Due to the side effects of widely known cisplatin and its derivative compounds, alternative metal-based drug discovery studies are still ongoing. In this study, the DNA-binding ability of Pd(II) and Pt(II) [...] Read more.
DNA has become the target of metal complexes in cancer drug discovery. Due to the side effects of widely known cisplatin and its derivative compounds, alternative metal-based drug discovery studies are still ongoing. In this study, the DNA-binding ability of Pd(II) and Pt(II) complexes of four phosphorus Schiff base ligands and four hydrazonoic-phosphines are investigated by using in silico analyses. Phosphorus Schiff base-Pd(II) complexes encoded as B1 and B2 with the best DNA-binding potential are synthesized and characterized. The DNA-binding potentials of these two new Pd(II) complexes are also investigated experimentally, and their antitumor properties are demonstrated in vitro in A549, MCF7, HuH7, and HCT116 cancer cells. The mechanisms of these metal complexes that kill the cells mentioned above in different activities are elucidated by flow cytometry apoptosis analysis and colony formation analysis The in silico binding energies of these two new palladium complexes ΔG (B1): −4.51 and ΔG (B2): −6.04 kcal/mol, and their experimental DNA-binding constants were found as Kb (B1): 4.24 × 105, Kb (B2): 4.98 × 105). The new complexes, which show different antitumor effects in different cells, are the least effective in HuH7 liver cells, while they showed the best antitumor properties in HCT116 colon cancer cells. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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19 pages, 3528 KiB  
Article
In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line
by Leide Laura Figueiredo Maciel, Marina Barreto Silva, Rafaela Oliveira Moreira, Ana Paula Cardoso, Christiane Fernandes, Adolfo Horn, Jr., João Carlos de Aquino Almeida and Milton Masahiko Kanashiro
Pharmaceutics 2022, 14(10), 2013; https://doi.org/10.3390/pharmaceutics14102013 - 22 Sep 2022
Cited by 10 | Viewed by 2832
Abstract
Two platinum complexes [Pt(HL3)Cl]·H2O (3) and [Pt(HL4)Cl]·H2O (4) containing α- and β-naphthyl groups, respectively, were investigated in more detail in vitro and in vivo for antineoplastic activity. The cytotoxicity activity induced by these platinum(II) [...] Read more.
Two platinum complexes [Pt(HL3)Cl]·H2O (3) and [Pt(HL4)Cl]·H2O (4) containing α- and β-naphthyl groups, respectively, were investigated in more detail in vitro and in vivo for antineoplastic activity. The cytotoxicity activity induced by these platinum(II) compounds against breast cancer (MDA-MB-231 and MCF-7), lung (A549), prostate (PC3), pancreas (BXPC-3), and normal peripheral blood mononuclear (PBMC) cells were evaluated by MTT assay. The cell viability MTT assay showed that complex (4) was more cytotoxic to all cancer cell lines tested and less cytotoxic against human PBMC. Therefore, complex (4) was selected to further investigate the mechanism of cytotoxic effects involved against MDA-MB-231 cell line (human triple-negative breast cancer). Sub-G1 analysis of the cell cycle showed that this complex induces cell death by apoptosis due to the cell loss of DNA content detected in flow cytometry. The cytotoxic effect induced by complex (4) was associated with the capability of the complex to induce mitochondrial membrane depolarization, as well as increase ROS levels and caspase activation, as a result of the activation of both extrinsic and intrinsic apoptosis pathways. Ultrastructural alterations were observed using scanning and transmission electron microscopy (SEM and TEM), such as membrane blebbing, filopodia reduction, empty mitochondrial matrix, and DNA fragmentation. Furthermore, complex (4) was tested in an MDA-MB-231 tumor nodule xenograft murine model and demonstrated a remarkable reduction in tumor size in BALB/c nude mice, when compared to the control animals. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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28 pages, 17339 KiB  
Article
Green Synthesis of Hexagonal Silver Nanoparticles Using a Novel Microalgae Coelastrella aeroterrestrica Strain BA_Chlo4 and Resulting Anticancer, Antibacterial, and Antioxidant Activities
by Reham Samir Hamida, Mohamed Abdelaal Ali, Zakiah Nasser Almohawes, Hadil Alahdal, Maha Abdullah Momenah and Mashael Mohammed Bin-Meferij
Pharmaceutics 2022, 14(10), 2002; https://doi.org/10.3390/pharmaceutics14102002 - 21 Sep 2022
Cited by 35 | Viewed by 3439
Abstract
Microalgae-mediated synthesis of nanoparticles (NPs) is an emerging nanobiotechnology that utilizes the biomolecular corona of microalgae as reducing and capping agents for NP fabrication. This study screened a novel microalgal strain for its potential to synthesize silver (Ag)-NPs and then assayed the biological [...] Read more.
Microalgae-mediated synthesis of nanoparticles (NPs) is an emerging nanobiotechnology that utilizes the biomolecular corona of microalgae as reducing and capping agents for NP fabrication. This study screened a novel microalgal strain for its potential to synthesize silver (Ag)-NPs and then assayed the biological activities of the NPs. Coelastrella aeroterrestrica strain BA_Chlo4 was isolated, purified, and morphologically and molecularly identified. Chemical composition of the algal extract was determined by GC-MS analysis. Ag-NPs were biosynthesized by C. aeroterrestrica BA_Chlo4 (C@Ag-NPs) and characterized using various techniques. Antiproliferative activity and the biocidal effect of C@Ag-NPs, C. aeroterrestrica algal extract, and chemically synthesized Ag-NPs (Ch@Ag-NPs) were explored, and the scavenging activity of C@Ag-NPs against free radicals was investigated. C@Ag-NPs were hexagonal, with a nanosize diameter of 14.5 ± 0.5 nm and a maximum wavelength at 404.5 nm. FTIR and GC-MS analysis demonstrated that proteins and polysaccharide acted as capping and reducing agents for C@Ag-NPs. X-ray diffraction, energy diffraction X-ray, and mapping confirmed the crystallinity and natural structure of C@Ag-NPs. The hydrodynamic diameter and charge of C@Ag-NPs was 28.5 nm and −33 mV, respectively. C@Ag-NPs showed significant anticancer activity towards malignant cells, with low toxicity against non-cancerous cells. In addition, C@Ag-NPs exhibited greater antioxidant activity and inhibitory effects against Gram-positive and -negative bacteria compared with the other tested treatments. These findings demonstrate, for first time, the potential of a novel strain of C. aeroterrestrica to synthesize Ag-NPs and the potent antioxidant, anticancer, and biocidal activities of these NPs. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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15 pages, 17945 KiB  
Article
Design, Synthesis, and Characterization of Novel Coordination Compounds of Benzimidazole Derivatives with Cadmium
by Anita Raducka, Marcin Świątkowski, Izabela Korona-Głowniak, Barbara Kaproń, Tomasz Plech, Małgorzata Szczesio, Katarzyna Gobis and Agnieszka Czylkowska
Pharmaceutics 2022, 14(8), 1626; https://doi.org/10.3390/pharmaceutics14081626 - 3 Aug 2022
Cited by 7 | Viewed by 2379
Abstract
Four complexes of Cd(II) with benzimidazole derivatives were synthesized and named C1, C2, C3, and C4. All coordination compounds were characterized through elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis coupled with mass spectrometry) (TG-MS), a cytotoxicity [...] Read more.
Four complexes of Cd(II) with benzimidazole derivatives were synthesized and named C1, C2, C3, and C4. All coordination compounds were characterized through elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis coupled with mass spectrometry) (TG-MS), a cytotoxicity assay (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide)), and computational chemical analysis for absorption, distribution, metabolism, and excretion (ADME). All of the obtained results are compatible and are consistent with the respective structures of the obtained compounds and their properties. The various techniques used allowed the determination of the composition, proposed structure of the compounds, their thermal stability and thermal properties, and the method of coordination between the metal (II) ion and the ligand. The ADME technique was also used to estimate the physicochemical and biological properties. The antitumor activity of the compounds was determined with an MTT assay on the glioblastoma (T98G), neuroblastoma (SK-N-AS), and lung adenocarcinoma (A549) cell lines, as well as normal human skin fibroblasts (CCD-1059Sk). Compound C2 was found to have potential antitumor properties and to be effective in inhibiting the growth of neuroblastoma cells. The antimicrobial activity of Cd complexes, free ligands, and reference drugs was tested against six strains of Gram-positive bacteria, five strains of Gram-negative rods, and three strains of yeasts. Compound C3 significantly increased activity against Gram-positive bacteria in comparison to the ligand. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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Review

Jump to: Research

31 pages, 1953 KiB  
Review
Metal and Metal Oxides Nanoparticles and Nanosystems in Anticancer and Antiviral Theragnostic Agents
by Tatyana I. Shabatina, Olga I. Vernaya, Nikolay L. Shimanovskiy and Mikhail Ya. Melnikov
Pharmaceutics 2023, 15(4), 1181; https://doi.org/10.3390/pharmaceutics15041181 - 7 Apr 2023
Cited by 27 | Viewed by 3403
Abstract
The development of antiviral treatment and anticancer theragnostic agents in recent decades has been associated with nanotechnologies, and primarily with inorganic nanoparticles (INPs) of metal and metal oxides. The large specific surface area and its high activity make it easy to functionalize INPs [...] Read more.
The development of antiviral treatment and anticancer theragnostic agents in recent decades has been associated with nanotechnologies, and primarily with inorganic nanoparticles (INPs) of metal and metal oxides. The large specific surface area and its high activity make it easy to functionalize INPs with various coatings (to increase their stability and reduce toxicity), specific agents (allowing retention of INPs in the affected organ or tissue), and drug molecules (for antitumor and antiviral therapy). The ability of magnetic nanoparticles (MNPs) of iron oxides and ferrites to enhance proton relaxation in specific tissues and serve as magnetic resonance imaging contrast agents is one of the most promising applications of nanomedicine. Activation of MNPs during hyperthermia by an external alternating magnetic field is a promising method for targeted cancer therapy. As therapeutic tools, INPs are promising carriers for targeted delivery of pharmaceuticals (either anticancer or antiviral) via magnetic drug targeting (in case of MNPs), passive or active (by attaching high affinity ligands) targeting. The plasmonic properties of Au nanoparticles (NPs) and their application for plasmonic photothermal and photodynamic therapies have been extensively explored recently in tumor treatment. The Ag NPs alone and in combination with antiviral medicines reveal new possibilities in antiviral therapy. The prospects and possibilities of INPs in relation to magnetic hyperthermia, plasmonic photothermal and photodynamic therapies, magnetic resonance imaging, targeted delivery in the framework of antitumor theragnostic and antiviral therapy are presented in this review. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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22 pages, 4882 KiB  
Review
Platinum-Nucleos(t)ide Compounds as Possible Antimetabolites for Antitumor/Antiviral Therapy: Properties and Perspectives
by Federica De Castro, Erika Stefàno, Erik De Luca, Michele Benedetti and Francesco Paolo Fanizzi
Pharmaceutics 2023, 15(3), 941; https://doi.org/10.3390/pharmaceutics15030941 - 14 Mar 2023
Cited by 7 | Viewed by 3008
Abstract
Nucleoside analogues (NAs) are a family of compounds which include a variety of purine and pyrimidine derivatives, widely used as anticancer and antiviral agents. For their ability to compete with physiological nucleosides, NAs act as antimetabolites exerting their activity by interfering with the [...] Read more.
Nucleoside analogues (NAs) are a family of compounds which include a variety of purine and pyrimidine derivatives, widely used as anticancer and antiviral agents. For their ability to compete with physiological nucleosides, NAs act as antimetabolites exerting their activity by interfering with the synthesis of nucleic acids. Much progress in the comprehension of their molecular mechanisms has been made, including providing new strategies for potentiating anticancer/antiviral activity. Among these strategies, new platinum-NAs showing a good potential to improve the therapeutic indices of NAs have been synthesized and studied. This short review aims to describe the properties and future perspectives of platinum-NAs, proposing these complexes as a new class of antimetabolites. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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29 pages, 3609 KiB  
Review
Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo
by Anastasiia S. Obozina, Elena N. Komedchikova, Olga A. Kolesnikova, Anna M. Iureva, Vera L. Kovalenko, Fedor A. Zavalko, Tatiana V. Rozhnikova, Ekaterina D. Tereshina, Elizaveta N. Mochalova and Victoria O. Shipunova
Pharmaceutics 2023, 15(1), 231; https://doi.org/10.3390/pharmaceutics15010231 - 10 Jan 2023
Cited by 13 | Viewed by 4310
Abstract
Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the [...] Read more.
Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way. We believe that the combination of the endless biomedical potential of protein carriers as nanoparticles and the standardized protein purification protocols will make significant progress in “magic bullet” creation possible, bringing modern biomedicine to a new level. In this review, we are focused on the currently existing platforms for targeted self-assembling protein nanoparticles based on transferrin, lactoferrin, casein, lumazine synthase, albumin, ferritin, and encapsulin proteins, as well as on proteins from magnetosomes and virus-like particles. The applications of these self-assembling proteins for targeted delivery in vitro and in vivo are thoroughly discussed, including bioimaging applications and different therapeutic approaches, such as chemotherapy, gene delivery, and photodynamic and photothermal therapy. A critical assessment of these protein platforms’ efficacy in biomedicine is provided and possible problems associated with their further development are described. Full article
(This article belongs to the Special Issue Novel Metal-Based Drugs for Anticancer and Antiviral Applications)
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