Methylsulfinyl hexyl isothiocyanate (6-MSITC) isolated from Eutrema japonicum is a promising candidate for the treatment of breast cancer, colorectal and stomach cancer, metabolic syndrome, heart diseases, diabetes, and obesity due to its anti-inflammatory and antioxidant properties. Also, its neuroprotective properties, improving cognitive function and protecting dopaminergic neurons, make it an excellent candidate for treating neurodegenerative diseases like dementia, Alzheimer\'s, and Parkinson\'s disease. 6-MSITC acts on many signaling pathways, such as PPAR, AMPK, PI3K/AKT/mTOR, Nrf2/Keap1-ARE, ERK1/2-ELK1/CHOP/DR5, and MAPK. However, despite the very promising results of in vitro and in vivo animal studies and a few human studies, the molecule has not yet been thoroughly tested in the human population. Nonetheless, wasabi should be classified as a \"superfood\" for the primary and secondary prevention of human diseases. This article reviews the current state-of-the-art research on 6-MSITC and its potential clinical uses, discussing in detail the signaling pathways activated by the molecule and their interactions.

Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1H)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1H)-one (benzoyl-)isothiocyanates, and the corresponding thioureide derivatives 8-11a-c were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC50 for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives 8,9a-c, in contrast to their acetyl-(benzoyl) derivatives and 10,11a-c, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9a has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC50 = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9c has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC50 = 12,94 mM). Compounds 8a, 8b, and 9b showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC50 against α-glucosidase for compounds 8a, 8b, and 9b was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds 8c, 10a, 10b, 10c, 11a, 11b, and 11c did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1H)-ones are promising candidates for the further modification and study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models.

UNASSIGNED: Diabetic kidney disease is a major contributor to end stage renal disease. A change in kidney oxygen homeostasis leading to decreased tissue oxygen tension is an important factor initiating alterations in kidney function in diabetes. However, the mechanism contributing to changed oxygen homeostasis is still unclear. Hyperglycemia-induced production of reactive oxygen species and an altered response to them have previously been demonstrated. In the present study, chronic treatment with DL-sulforaphane to induce nuclear factor erythroid 2-related factor 2 (Nrf2) expression, a master transcriptional regulator binding to antioxidant response elements inducing increased protection against reactive oxygen species, is studied.
UNASSIGNED: Sprague-Dawley rats were made diabetic using streptozotocin and either left untreated or received daily subcutaneous injections of DL-sulforaphane for 4 weeks. Age-matched non-diabetic rats served as controls. After 4 weeks of treatment, rats were anesthetized using thiobutabarbital, and kidney functions were studied in terms of glomerular filtration rate (GFR), renal blood flow (RBF), sodium transport, kidney oxygen consumption, and kidney oxygen tension. Mitochondria was isolated from kidney cortical tissue and investigated using high-resolution respirometry.
UNASSIGNED: GFR was increased in diabetics but not RBF resulting in increased filtration fraction in diabetics. DL-sulforaphane treatment did not affect RBF and GFR in controls but decreased the same parameters in diabetics. Increased GFR resulted in increased sodium transport and oxygen consumption, hence decreased efficiency in diabetics compared to controls. Increased oxygen consumption in diabetics resulted in decreased cortical tissue oxygen tension. DL-sulforaphane treatment decreased oxygen consumption in diabetics, whereas transport efficiency was not significantly affected. DL-sulforaphane treatment increased cortical pO2 in diabetics.
UNASSIGNED: DL-sulforaphane treatment affects renal hemodynamics, improving cortical oxygen tension but not mitochondrial efficiency.

Exposure to 2.45 GHz electromagnetic radiation (EMR) emitted from commonly used devices has been reported to induce oxidative stress in several experimental models. Our study aims to evaluate the efficacy of sulforaphane, a well-known natural product, in preventing radiation-induced toxic effects caused by a 24 h exposure of SH-SY5Y neuronal-like cells and peripheral blood mononuclear cells (PBMCs) to 2.45 GHz EMR. Cells were exposed to radiation for 24 h in the presence or absence of sulforaphane at different concentrations (5-10-25 µg/mL). Cell viability, mitochondrial activity alterations, the transcription and protein levels of redox markers, and apoptosis-related genes were investigated. Our data showed a reduction in cell viability of both neuronal-like cells and PBMCs caused by EMR exposure and a protective effect of 5 µg/mL sulforaphane. The lowest sulforaphane concentration decreased ROS production and increased the Mitochondrial Transmembrane Potential (Δψm) and the NAD+/NADH ratio, which were altered by radiation exposure. Sulforaphane at higher concentrations displayed harmful effects. The hormetic behavior of sulforaphane was also evident after evaluating the expression of genes coding for Nrf2, SOD2, and changes in apoptosis markers. Our study underlined the vulnerability of neuronal-like cells to mitochondrial dysfunction and oxidative stress and the possibility of mitigating these effects by supplementation with sulforaphane. To our knowledge, there are no previous studies about the effects of SFN on these cells when exposed to 2.45 GHz electromagnetic radiation.

Allyl isothiocyanate (AITC) is the pungent ingredient of brassica species, used as a food additive and flavoring agent, including condiments such as wasabi, horseradish, and mustard. Currently, there is much evidence that AITC modulates glucose and lipids metabolism. Interestingly, AITC has been shown to improve glycaemia, and insulin action along with the induction of a deepened decline in blood insulin levels in T2DM rats. Therefore, in the present study, we characterized the role of AITC at a wide concentration range (5, 10, 25, 50, 100 μM) in controlling viability, proliferation, apoptosis, mitochondrial condition, mRNA expression of encoding pancreatic and duodenal homeobox 1 (Pdx1), and Ins1, Ins2 genes, and insulin content in INS-1E cells. The INS-1E cell line is a suitable, and well-characterized model to study beta cell functions. We demonstrate that AITC reduced the viability (p≤0.001) (also in the presence of transient receptor potential cation subfamily A member 1 (TRPA1) selective antagonist; HC-030031; p≤0.05), and proliferation of INS-1E cells (p≤0.001). AITC evoked a significant reduction of mitochondrial membrane potential (p≤0.01) and decreased the intracellular level of adenosine triphosphate (ATP) (p≤0.001) without influence on reactive oxygen species (ROS) level. Additionally, AITC inhibited the insulin mRNA expression (p≤0.001) in INS-1E cells along with insulin content (p≤0.05). Mitochondrial dysfunction is proposed to be a significant disruption mechanism of AITC in INS-1E cells, and it was independent of ROS, and the influx of external calcium.

Amide bonds are one of the most prevalent phenomena in nature and are utilized frequently in drug and material design. However, forming amide bonds is not always efficient or high yielding, particularly when the amine used to conjugate to a carboxylic acid is a weak nucleophile. This limitation precludes many useful amino compounds from participating in conjugation reactions to form amides. A particularly valuable amino compound, which is also a very weak nucleophile, is the amino porphyrin, valued for its role as a photosensitizer, fluorescent agent, catalyst, or, upon metalation, even a very efficient contrast agent for magnetic resonance imaging (MRI). In this work, we propose fast and high-yield coupling of an unreactive amine - the amino porphyrin - to carboxylic acid via isothiocyanate conjugation. Reactions can be achieved in one step at room temperature in one hour, achieving quantitative conversion and near perfect selectivity. Both metalated and unmetalated porphyrin, as well as fluorescein isothiocyanate (FITC), demonstrated efficient conjugation. To illustrate the value of the proposed method, we created a new blood-pool MRI contrast agent that reversibly binds to serum albumin. This new blood-pool agent, known as MITC-Deox (MRI isothiocyanate that links with deoxycholic acid), substantially reduced T1 relaxation times in blood vessels in mice, remained stable for 1 hour, cleared from blood by 24 hours, and was eliminated from the body after 4 days. The proposed method for efficient amide formation is a superior alternative to existing coupling methods, opening a door to novel synthesis of MRI contrast agents and beyond.

Multidrug-resistant (MDR) Staphylococcus aureus infections significantly threaten global health. With rising resistance to current antibiotics and limited solutions, the urgent discovery of new, effective, and affordable antibacterials with low toxicity is imperative to combat diverse MDR S. aureus strains. Hence, in this study, we introduce an in silico phytochemical-based approach for discovering novel antibacterial agents, underscoring the potential of computational approaches in therapeutic discovery. Glucomoringin Isothiocyanate (GMG-ITC) from Moringa oleifera Lam. is one of the phytochemical compounds with several biological activities, including antimicrobial, anti-inflammatory, and antioxidant activities, and is also effective against S. aureus. This study focuses on screening GMG-ITC as a potential drug candidate to combat MDR S. aureus infections through a molecular docking approach. Moreover, interaction amino acid analysis, in silico pharmacokinetics, compound target prediction, pathway enrichment analysis and molecular dynamics (MD) simulations were conducted for further investigation. Molecular docking and interaction analysis showed strong binding affinity towards S. aureus lipase, dihydrofolate reductase, and other MDR S. aureus proteins, including penicillin-binding protein 2a, MepR, D-Ala:D-Ala ligase, and RPP TetM, through hydrophilic and hydrophobic interactions. GMG-ITC also showed a strong binding affinity to cyclooxygenase-2 and FAD-dependent NAD(P)H oxidase, suggesting that it is a potential anti-inflammatory and antioxidant candidate that may eliminate inflammation and oxidative stress associated with S. aureus infections. MD simulations validated the stability of the GMG-ITC molecular interactions determined by molecular docking. In silico pharmacokinetic analysis highlights its potency as a drug candidate, showing strong absorption, distribution, and excretion properties in combination with low toxicity. It acts as an active protease and enzyme inhibitor with moderate activity against GPCR ligands, ion channels, nuclear receptor ligands, and kinases. Enrichment analysis further elucidated its involvement in important biological, molecular, and cellular functions with potential therapeutic applications in diseases like cancer, hepatitis B, and influenza. Results suggest that GMG-ITC is an effective antibacterial agent that could treat MDR S. aureus-associated infections.

Growing evidence indicates that the intake of trans fatty acids (TFAs) increases the risk of numerous diseases, such as cardiovascular diseases. Recently, our group found that certain natural sulfur compounds (allyl isothiocyanate [AITC] and diallyl disulfide [DADS]) promote cis to trans isomerization of fatty acid esters during heat treatment. However, little information is available on the fatty acid isomerization with them. In this study, we investigated the effects of oxygen and α-tocopherol (antioxidant) on isomerization of oleic acid (18:1) methyl ester (OA-ME) in the presence of AITC and DADS. Furthermore, the effect of the simultaneous use of AITC and DADS was evaluated. Our results indicate that oxygen enhances the AITC-induced trans isomerization, and DADS was found to promote trans isomerization but inhibit AITC-induced trans isomerization during heating. Both AITC- and DADS-induced trans isomerization were inhibited by α-tocopherol. These results indicate that the trans isomerization of fatty acids induced by sulfur compounds can be controlled by devising a cooking process and the food ingredients used together.

Triple-negative breast cancer (TNBC) represents aggressive phenotype with limited treatment options due to the lack of drug targets. Natural compounds are extensively studied regarding their potential to alter the efficacy of cancer treatment Among them sulforaphane - an isothiocyanate of natural origin, was shown to be a hormetic compound, that may exert divergent effects: cytoprotective or cytotoxic depending on its concentrations. Thus, the aim of this study was to determine the effect of its low, dietary concentrations on the proliferation and migration of the TNBC cells in the in vivo and in vitro 2D and 3D model. Results of the in vivo experiment showed up to 31% tumor growth inhibition after sulforaphane treatment associated with lowered proliferating potential of cancer cells, reduced areas of necrosis, and changed immune cell type infiltration, showing less malignant type of tumor in contrast to the non-treated group. Also, the study revealed that sulforaphane decreased the number of lung metastases. The in vitro study confirmed that SFN inhibited cell migration, but only in cells derived from 3D spheroids, not from 2D in vitro cultures. The results show a specific role of sulforaphane in the case of cells released from the TNBC primary tumor and its environment.

In the present study, one mononuclear Cu(II) [CuL(SCN)] (1) and one mononuclear Co(II) [CoLN3] (2) complexes, with a Schiff base ligand (HL) formed by condensation of 2-picolylamine and salicylaldehyde, have been successfully developed and structurally characterized. The square planer geometry of both complexes is fulfilled by the coordination of one deprotonated ligand and one ancillary ligand SCN-(1) or N3-(2) to the metal centre. Binding affinities of both complexes with deoxyribonucleic acid (DNA) and human serum albumin (HSA) are investigated using several biophysical and spectroscopic techniques. High values of the macromolecule-complex binding constants and other results confirm the effectiveness of both complexes towards binding with DNA and HSA. The determined values of the thermodynamic parameters support spontaneous interactions of both complexes with HSA, while fluorescence displacement and DNA melting studies establish groove-binding interactions with DNA for both complexes 1 and 2. The molecular modelling study validates the experimental findings. Both complexes are subjected to an MTT test establishing the anticancer property of complex 1 with lower risk to normal cells, confirmed by the IC50 values of the complex for HeLa cancer cells and HEK normal cells. Finally, a nuclear staining analysis reveals that the complexes have caused apoptotic cell death.