Gold and Silver Complexes in the Treatment of Diseases 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 6280

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Department of Pharmacology and Physiology, Legal and Forensic Medicine, Physiology Unit, Faculty of Veterinary Medicine, University of Zaragoza, 50013 Zaragoza, Spain
Interests: intestinal absorption of nutrients; sepsis status (LPS, cytokines and inflammation); plant extracts and olive oil (squalene) for therapeutic purposes; encapsulation of plant extracts to improve their bioavailability; antioxidant and anti-inflammatory properties of plant extracts; antioxidant and anti-inflammatory markers; studies (modulators, pathways and targets) of apoptosis, necroptosis and autophagy; cell culture; cancer (mainly colon cancer) and diseases related to oxidative stress (cardiovascular, osteoarthritis and cancer); chemotherapeutics (gold complexes)
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Special Issue Information

Dear Colleagues,

At present, metal pharmaceuticals offer a new perspective in pharmacology and medicine. The growing development of so-called bioinorganic chemistry based on new drugs derived from metal complexes opens new possibilities in the treatment of diseases. The development of this new field began with the discovery of cisplatin as an effective antitumor. Other metal complexes such as gold and silver have been used since ancient times for their therapeutic properties. However, the rational use of gold in medicine began in the early 1920s with the discovery of the inhibitory properties of gold cyanine in the tuber bacillus. So far, various diseases have been treated with gold derivatives, including tuberculosis and rheumatoid arthritis. In recent decades, gold complexes have been tested against HIV for the treatment of AIDS, acute forms of chronic asthma, and pemphigus (an autoimmune skin disease) and in the treatment of malaria, Chagas disease, and cancer. On the other hand, silver complexes have been used in the treatment of childhood blindness (ophthalmia neonatorum) and as antimicrobial agents for many years, and their antitumor potential is currently being studied. In recent years, the use of metal complexes as chemotherapeutic agents is gaining importance. In this sense, the choice of the ligand is especially important since it can improve silver’s biological properties, such as the biodistribution, activity, and selectivity of the compound in relation to its lipophilic–hydrophilic balance, and in the case of silver, it can also affect its stability. Likewise, the use of nanoparticles as chemotherapeutic agents to transport metal complexes is beginning to be investigated.

This Special Issue may publish original research papers and reviews on aspects related to gold and silver complexes in the treatment of diseases, highlighting the mechanism of action and targets involved in its therapeutic properties.

Dr. María Jesús Rodríguez-Yoldi
Guest Editor

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Keywords

  • gold complex
  • silver complex
  • ligands
  • health benefits
  • action mechanisms
  • targets

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Published Papers (4 papers)

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Research

21 pages, 4158 KiB  
Article
Heteronuclear Complexes with Promising Anticancer Activity against Colon Cancer
by Elena Atrián-Blasco, Javier Sáez, Maria Jesús Rodriguez-Yoldi and Elena Cerrada
Biomedicines 2024, 12(8), 1763; https://doi.org/10.3390/biomedicines12081763 - 5 Aug 2024
Viewed by 740
Abstract
This study investigates the activity of novel gold(I) and copper(I)/zinc(II) heteronuclear complexes against colon cancer. The synthesised heteronuclear Au(I)-Cu(I) and Au(I)-Zn(II) complexes were characterised and evaluated for their anticancer activity using human colon cancer cell lines (Caco-2). The complexes exhibited potent cytotoxicity, with [...] Read more.
This study investigates the activity of novel gold(I) and copper(I)/zinc(II) heteronuclear complexes against colon cancer. The synthesised heteronuclear Au(I)-Cu(I) and Au(I)-Zn(II) complexes were characterised and evaluated for their anticancer activity using human colon cancer cell lines (Caco-2). The complexes exhibited potent cytotoxicity, with IC50 values in the low micromolar range, and effectively induced apoptosis in cancer cells. In the case of complex [Cu{Au(Spy)(PTA)}2]PF6 (2), its cytotoxicity is ×10 higher than its mononuclear precursor, while showing low cytotoxicity towards differentiated healthy cells. Mechanistic studies revealed that complex 2 inhibits the activity of thioredoxin reductase, a key enzyme involved in redox regulation, leading to an increase in reactive oxygen species (ROS) levels and oxidative stress, in addition to an alteration in DNA’s tertiary structure. Furthermore, the complexes demonstrated a strong binding affinity to bovine serum albumin (BSA), suggesting the potential for effective drug delivery and bioavailability. Collectively, these findings highlight the potential of the investigated heteronuclear Au(I)-Cu(I) and Au(I)-Zn(II) complexes as promising anticancer agents, particularly against colon cancer, through their ability to disrupt redox homeostasis and induce oxidative stress-mediated cell death. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases 2.0)
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17 pages, 4523 KiB  
Article
Silver(I) Bromide Phosphines Induce Mitochondrial-Mediated Apoptosis in Malignant Human Colorectal Cells
by Kim Elli Roberts, Zelinda Engelbrecht, Kariska Potgieter, Reinout Meijboom and Marianne Jacqueline Cronjé
Biomedicines 2023, 11(10), 2794; https://doi.org/10.3390/biomedicines11102794 - 14 Oct 2023
Cited by 3 | Viewed by 1482
Abstract
Due to its emerging resistance to current therapies, colon cancer remains one of the most difficult types of cancer to treat. Silver, a non-invasive metal, is well-known for its antimicrobial and anti-cancer properties. Two novel silver(I) phosphine complexes, [silver(I) diphenyl-2-pyridylphosphine]Br (1) [...] Read more.
Due to its emerging resistance to current therapies, colon cancer remains one of the most difficult types of cancer to treat. Silver, a non-invasive metal, is well-known for its antimicrobial and anti-cancer properties. Two novel silver(I) phosphine complexes, [silver(I) diphenyl-2-pyridylphosphine]Br (1) and [silver(I) is 4-(dimethylamino)phenyldiphenylphosphine]Br (2), were synthesized and characterized by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance (1H, 13C, 31P). To assess the complexes’ potentials as antiproliferative agents, experiments were conducted on human colorectal cancer cells (HT-29) in vitro. The evaluation involved the analysis of morphological changes, the performance of an alamarBlue® proliferation assay, and the undertaking of flow cytometric analyses to detect mitochondrial alterations. Complex 1 displayed superior selectivity and significant inhibitory effects on malignant HT-29 cells while exhibiting minimal toxicity towards two non-malignant HEK-293 and MRHF cells. Moreover, after 24 h of treatment, complex 1 (IC50, 7.49 µM) demonstrated higher efficacy in inhibiting cell proliferation compared with complex 2 (IC50, 21.75 µM) and CDDP (IC50, 200.96 µM). Flow cytometric studies indicated that complex 1 induced regulated cell death, likely through mitochondrial-mediated apoptosis. Treatment with complex 1 induced morphological changes indicative of apoptosis, which includes membrane blebbing, PS externalization, increased levels of reactive oxygen species (ROS) and mitochondrial membrane depolarization (ΔΨm). These observations suggest that complex 1 targets the mitochondria and holds promise as a novel metal-based anti-cancer therapeutic for the selective treatment of colorectal cancer. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases 2.0)
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16 pages, 1761 KiB  
Article
Synthesis, Characterization, and Anticancer Activity of Phosphanegold(i) Complexes of 3-Thiosemicarbano-butan-2-one Oxime
by Sani A. Zarewa, Lama Binobaid, Adam A. A. Sulaiman, Homood M. As Sobeai, Moureq Alotaibi, Ali Alhoshani and Anvarhusein A. Isab
Biomedicines 2023, 11(9), 2512; https://doi.org/10.3390/biomedicines11092512 - 12 Sep 2023
Cited by 2 | Viewed by 1833
Abstract
Four novel phosphanegold(I) complexes of the type [Au(PR3)(DMT)].PF6 (14) were synthesized from 3-Thiosemicarbano-butan-2-one oxime ligand (TBO) and precursors [Au(PR3)Cl], (where R = methyl (1), ethyl (2), tert-butyl (3), [...] Read more.
Four novel phosphanegold(I) complexes of the type [Au(PR3)(DMT)].PF6 (14) were synthesized from 3-Thiosemicarbano-butan-2-one oxime ligand (TBO) and precursors [Au(PR3)Cl], (where R = methyl (1), ethyl (2), tert-butyl (3), and phenyl (4)). The resulting complexes were characterized by elemental analyses and melting point as well as various spectroscopic techniques, including FTIR and (1H, 13C, and 31P) NMR spectroscopy. The spectroscopic data confirmed the coordination of TBO ligands to phosphanegold(I) moiety. The solution chemistry of complexes 14 indicated their stability in both dimethyl sulfoxide (DMSO) and a mixture of EtOH:H2O (1:1). In vitro cytotoxicity of the complexes was evaluated relative to cisplatin using an MTT assay against three different cancer cell lines: HCT116 (human colon cancer), MDA-MB-231 (human breast cancer), and B16 (murine skin cancer). Complexes 2, 3, and 4 exhibited significant cytotoxic effects against all tested cancer cell lines and showed significantly higher activity than cisplatin. To elucidate the mechanism underlying the cytotoxic effects of the phosphanegold(I) TBO complexes, various assays were employed, including mitochondrial membrane potential, ROS production, and gene expression analyses. The data obtained suggest that complex 2 exerts potent anticancer activity against breast cancer cells (MDA-MB-231) through the induction of oxidative stress, mitochondrial dysfunction, and apoptosis. Gene expression analyses showed an increase in the activity of the proapoptotic gene caspase-3 and a reduction in the activity of the antiapoptotic gene BCL-xL, which supported the findings that apoptosis had occurred. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases 2.0)
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15 pages, 3484 KiB  
Article
Biological Performance of Primary Dental Pulp Stem Cells Treated with Gold Nanoparticles
by Duaa Abuarqoub, Nouf Mahmoud, Walhan Alshaer, Marwa Mohammad, Abed Alqader Ibrahim, Mairvat Al-Mrahleh, Mohammad Alnatour, Dana A. Alqudah, Ezaldeen Esawi and Abdalla Awidi
Biomedicines 2023, 11(9), 2490; https://doi.org/10.3390/biomedicines11092490 - 8 Sep 2023
Cited by 1 | Viewed by 1609
Abstract
Gold nanoparticles (AuNPs) are one of the most stable nanoparticles that have been prevalently used as examples for biological and biomedical applications. Herein, we evaluate the effect of AuNPs on the biological processes of dental pulp stem cells derived from exfoliated deciduous teeth [...] Read more.
Gold nanoparticles (AuNPs) are one of the most stable nanoparticles that have been prevalently used as examples for biological and biomedical applications. Herein, we evaluate the effect of AuNPs on the biological processes of dental pulp stem cells derived from exfoliated deciduous teeth (SHED). Two different shapes of PEGylated AuNPs, rods (AuNR-PEG) and spheres (AuNS-PEG), were prepared and characterized. SHED cells were treated with different concentrations of AuNR-PEG and AuNS-PEG to determine their effect on the stemness profile of stem cells (SCs), proliferation, cytotoxicity, cellular uptake, and reactive oxygen species (ROS), for cells cultured in media containing-fetal bovine serum (FBS) and serum-free media (SFM). Our results showed that both nanoparticle shapes maintained the expression profile of MSC surface markers. Moreover, AuNS-PEG showed a stimulatory effect on the proliferation rate and lower toxicity on SHED, compared to AuNR-PEG. Higher concentrations of 0.5–0.125 nM of AuNR-PEG have been demonstrated to cause more toxicity in cells. Additionally, cells treated with AuNPs and cultured in FBS showed a higher proliferative rate and lower toxicity when compared to the SFM. For cellular uptake, both AuNS-PEG and AuNR-PEG were uptaken by treated cells efficiently. However, cells cultured in SFM media showed a higher percentage of cellular uptake. For ROS, AuNR-PEG showed a significant reduction in ROS at lower concentrations (<0.03 nM), while AuNS-PEG did not show any significant difference compared to the control untreated cells. Thus, our results give evidence about the optimum concentration and shape of AuNPs that can be used for the differentiation of stem cells into specific cell lineages in tissue engineering and regenerative medicine. Full article
(This article belongs to the Special Issue Gold and Silver Complexes in the Treatment of Diseases 2.0)
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