Amine-substituted heterocyclic thioamide Cu(I) and Ag(I) complexes as effective anticancer and antibacterial agents targeting the periplasm of E. coli bacteria.

Metal complexes showing dual activity against cancer and bacterial infections are currently the focus of significant interest for their potential in treating life-threatening diseases. Aiming to investigate the impact of ligand substituents on these bioactivity properties of Group 11 d metal complexes, we herein present a series of mononuclear Cu(I) and Ag(I) complexes featuring the bis-NH-substituted heterocyclic thioamide dap2SH (=4,6-diaminopyrimidine-2-thione), namely [AgCl(dap2SH)(PPh)] (1), [CuBr(dap2SH)(PPh)] (2), [CuBr(dap2SH)(xantphos)] (3), [Ag(dap2S)(xantphos)] (4), and [Cu(dap2S)(xantphos)] (5) (xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene). Complexes were characterized by means of different physicochemical methods (i.

Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis by Modulating the Expression of Apoptotic Genes, Members of Polycomb Repressive Complex 2, and Levels of Tri-Methylating Lysine 27 at Histone 3 in Human Malignant Melanoma Cells.

In this study, we utilized an in vitro model consisting of human malignant melanoma as well as non-tumorigenic immortalized keratinocyte cells with the aim of characterizing the therapeutic effectiveness of the clinical epigenetic drug Tazemetostat alone or in combination with various isothiocyanates. In doing so, we assessed markers of cell viability, apoptotic induction, and expression levels of key proteins capable of mediating the therapeutic response. Our data indicated, for the first time, that Tazemetostat caused a significant decrease in viability levels of malignant melanoma cells in a dose- and time-dependent manner via the induction of apoptosis, while non-malignant keratinocytes were more resistant.

The Predictive Value of 8-Hydroxy-Deoxyguanosine (8-OHdG) Serum Concentrations in Irradiated Non-Small Cell Lung Carcinoma (NSCLC) Patients.

Ionizing radiation is strongly linked to direct or indirect DNA damage, as with the production of reactive oxygen species (ROS), which in turn produce DNA damage products, such as 8-hydroxy-2-deoxyguanosine (8-OHdG). In this study, we aimed to investigate the formation of 8-OHdG after irradiation in patients with non-small cell cancer (NSCLC) and its use as a biomarker. Sixteen patients with squamous and thirty-six patients with non-squamous pathology were included.

N-heterocyclic-carbene vs diphosphine auxiliary ligands in thioamidato Cu(I) and Ag(I) complexes towards the development of potent and dual-activity antibacterial and apoptosis-inducing anticancer agents.

Group 11 metal complexes exhibit promising antibacterial and anticancer properties which can be further enhanced by appropriate ligands. Herein, a series of mononuclear thioamidato Cu(I) and Ag(I) complexes bearing either a diphosphine (P^P) or a N-heterocyclic carbene (NHC) auxiliary ligand (L) was synthesized, and the impact of the co-ligand L on the in vitro antibacterial and anticancer properties of their complexes was assessed. All complexes effectively inhibited the growth of various bacterial strains, with the NHC-Cu(I) complex found to be particularly effective against the Gram (+) bacteria (IC = 1-4 μg mL).

Chemical Characterization and Biological Evaluation of Extracts in an In Vitro Model of Human Malignant Melanoma.

Malignant melanoma is an aggressive type of skin cancer characterised by high metastatic capacity and mortality rate. On the other hand, is known for its medicinal properties, including its anticancer potency. In this context, we aimed to (i) isolate various extracts of , (ii) characterize their phytochemical content, and (iii) determine their cytotoxic potential in an in vitro model of human malignant melanoma.

A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors.

The rubric of immune-related (ir) diabetes mellitus (DM) (irDM) encompasses various hyperglycemic disorders related to immune checkpoint inhibitors (ICPis). Beyond sharing similarities with conventional DM, irDM is a distinct, yet important, entity. The present narrative review provides a comprehensive overview of the literature regarding irDM published in major databases from January 2018 until January 2023.

Synthesis and antiproliferative activities of steroidal lactam conjugates bearing a new nitrogen mustard.

Alkylating agents are potent anticancer compounds that exert their anticancer properties through the inhibition of cell replication and transcription leading to cell death. Despite the numerous benefits, these agents also have serious drawbacks such as their high toxicity and low specificity towards cancer cells. As previously reported by our group, conjugation of alkylating agents with azasteroids can reduce their systemic toxicity and enhance their anticancer activity.

Inhibition of Cancer Cell Proliferation and Bacterial Growth by Silver(I) Complexes Bearing a CH-Substituted Thiadiazole-Based Thioamide.

Ag(I) coordination compounds have recently attracted much attention as antiproliferative and antibacterial agents against a wide range of cancer cell lines and pathogens. The bioactivity potential of these complexes depends on their structural characteristics and the nature of their ligands. Herein, we present a series of four Ag(I) coordination compounds bearing as ligands the CH-substituted thiadiazole-based thioamide 5-methyl-1,3,4-thiadiazole-2-thiol (mtdztH) and phosphines, i.

Polyphenolics, glucosinolates and isothiocyanates profiling of aerial parts of (Watercress).

Watercress () is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode.

Refining personalized diagnosis, treatment and exploitation of hypothyroidism related to solid nonthyroid cancer.

Hypothyroidism in the setting of cancer is a puzzling entity due to the dual role of the thyroid hormones (TH) in cancer - promoting versus inhibitory - and the complexity of the hypothyroidism itself. The present review provides a comprehensive overview of the personalized approach to hypothyroidism in patients with solid nonthyroid cancer, focusing on current challenges, unmet needs and future perspectives. Major electronic databases were searched from January 2011 until March 2022.

The continuum of care of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors: time for an intimate collaboration between oncologists and endocrinologists.

Introduction: Hypothyroidism is a common adverse event of various anticancer treatment modalities, constituting a notable paradigm of the integration of the endocrine perspective into precision oncology.

Areas Covered: The present narrative review provides a comprehensive and updated overview of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors. A study search was conducted on the following electronic databases: PubMed, Google Scholar, Scopus.

The Clinical Relevance of Hypothyroidism in Patients with Solid Non-Thyroid Cancer: A Tantalizing Conundrum.

Hypothyroidism in patients with solid non-thyroid cancer is a tantalizing entity, integrating an intriguing thyroid hormones (THs)-cancer association with the complexity of hypothyroidism itself. The present narrative review provides a comprehensive overview of the clinical relevance of hypothyroidism in solid non-thyroid cancer. Hypothyroidism in patients with solid non-thyroid cancer is reminiscent of hypothyroidism in the general population, yet also poses distinct challenges due to the dual role of THs in cancer: promoting versus inhibitory.

Assessment of Methodological Pipelines for the Determination of Isothiocyanates Derived from Natural Sources.

Isothiocyanates are biologically active secondary metabolites liberated via enzymatic hydrolysis of their sulfur enriched precursors, glucosinolates, upon tissue plant disruption. The importance of this class of compounds lies in their capacity to induce anti-cancer, anti-microbial, anti-inflammatory, neuroprotective, and other bioactive properties. As such, their isolation from natural sources is of utmost importance.

Evaluation of Bioactive Properties of Lipophilic Fractions of Edible and Non-Edible Parts of (Watercress) in a Model of Human Malignant Melanoma Cells.

Watercress is an enriched source of phenethyl isothiocyanate (PEITC), among other phytochemicals, with an antioxidant capacity. The aim of this study was to (i) chemically characterize and () biologically evaluate the profile of the main health-promoting compounds contained in edible (i.e.

The Intriguing Thyroid Hormones-Lung Cancer Association as Exemplification of the Thyroid Hormones-Cancer Association: Three Decades of Evolving Research.

Exemplifying the long-pursued thyroid hormones (TH)-cancer association, the TH-lung cancer association is a compelling, yet elusive, issue. The present narrative review provides background knowledge on the molecular aspects of TH actions, with focus on the contribution of TH to hallmarks of cancer. Then, it provides a comprehensive overview of data pertinent to the TH-lung cancer association garnered over the last three decades and identifies obstacles that need to be overcome to enable harnessing this association in the clinical setting.

Chemical and Biological Characterization of the Anticancer Potency of in a Model of Human Malignant Melanoma.

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma.

Charting the Unknown Association of COVID-19 with Thyroid Cancer, Focusing on Differentiated Thyroid Cancer: A Call for Caution.

Background: Conceived of as the "silver lining" of the dark cloud of the coronavirus disease 2019 (COVID-19) pandemic, lessons taught by this catastrophe should be leveraged by medical authorities and policy makers to optimize health care globally. A major lesson is that resilient health systems should absorb sudden shocks incited by overwhelming health emergencies without compromising the continuum of care of chronic diseases, especially of cancer.

Methods: The present review dissects the association between COVID-19 and thyroid cancer (TC), especially with differentiated TC (DTC), focusing on available data, knowledge gaps, current challenges, and future perspectives.

The Continuum of Thyroid Disorders Related to Immune Checkpoint Inhibitors: Still Many Pending Queries.

Background: Until more data are available to shed light on the thyroid disorders related to immune checkpoint inhibitors (ICPi) implemented for the treatment of hematological malignancies, the decision-making is guided by pertinent data derived mostly from solid tumors.

Methods: The present review provides a comprehensive and updated overview of the thyroid disorders related to ICPi, namely to inhibitors of cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death (PD) 1 (PD-1), and the ligand of the latter (PD-L1).

Results: With the increasing recognition of ir thyroid disorders, many outstanding issues have emerged.

Synthesis and Biological Evaluation of a c(RGDyK) Peptide Conjugate of SRPIN803.

In the present study, SRPIN803 and c(RGDyK)-SRPIN803 hybrid compounds were efficiently synthesized and evaluated for their stability in human plasma and buffers of pH 7.4 and 5.2.

Cytocidal Antitumor Effects against Human Ovarian Cancer Cells Induced by B-Lactam Steroid Alkylators with Targeted Activity against Poly (ADP-Ribose) Polymerase (PARP) Enzymes in a Cell-Free Assay.

We evaluated three newly synthesized B-lactam hybrid homo-aza-steroidal alkylators (ASA-A, ASA-B and ASA-C) for their PARP1/2 inhibition activity and their DNA damaging effect against human ovarian carcinoma cells. These agents are conjugated with an alkylating component (POPA), which also served as a reference molecule (positive control), and were tested against four human ovarian cell lines in vitro (UWB1.289 + BRCA1, UWB1.

Effects of a Novel Thiadiazole Derivative with High Anticancer Activity on Cancer Cell Immunogenic Markers: Mismatch Repair System, PD-L1 Expression, and Tumor Mutation Burden.

Microsatellite instability (MSI), tumor mutation burden (TMB), and programmed cell death ligand-1 (PD-L1) are particularly known as immunotherapy predictive biomarkers. MSI and TMB are closely related to DNA mismatch repair (MMR) pathway functionality, while the PD-L1 checkpoint mediates cancer cell evasion from immune surveillance via the PD-L1/PD-1 axis. Among all the novel triazolo[3,4-]thiadiazole derivatives, the compound KA39 emerged as the most potent anticancer agent.

Benzyl and phenethyl isothiocyanates as promising epigenetic drug compounds by modulating histone acetylation and methylation marks in malignant melanoma.

Melanoma is an aggressive skin cancer with increasing incidence rates globally. On the other hand, isothiocyanates are derived from cruciferous vegetables and are known to exert a wide range of anti-cancer activities including, among others, their ability to interact with the epigenome in order to supress cancer progression. The aim of this study was to determine the role of phenethyl and benzyl isothiocyanates in modulating histone acetylation and methylation as a potential epigenetic therapeutic strategy in an in vitro model of malignant melanoma.

Anticancer Activity of Triazolo-Thiadiazole Derivatives and Inhibition of AKT1 and AKT2 Activation.

The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice.