Search Results (516)

Objectives: To investigate the efficacy and underlying mechanisms of IBCar’s biological activity in breast cancer models, both in cell culture and in mice, and to compare its effects on cancer versus normal cells. Methods: The cytotoxicity of IBCar was evaluated using the MTS assay to assess metabolic activity and the clonogenic assay to determine reproductive integrity. The impact of IBCar on microtubule integrity, mitochondrial function, and multiple signaling pathways was analyzed using Western blotting, microarray analysis, and live cell imaging. The therapeutic effectiveness of orally administered IBCar was assessed in a transgenic mouse model of Luminal B breast cancer and in mice implanted with subcutaneous triple-negative breast cancer xenografts. Results: IBCar demonstrated potent cytotoxicity across a diverse panel of breast cancer cell lines, including those with mutant or wild-type TP53, and cell lines with short and long doubling times. Comparative analysis revealed distinct responses between normal and cancer cells, including differences in IBCar’s effects on the mitochondrial membrane potential, endoplasmic reticulum stress and activation of cell death pathways. In breast cancer cells, IBCar was cytotoxic at nanomolar concentrations, caused irreversible microtubule depolymerization leading to sustained mitochondrial dysfunction, endoplasmic reticulum stress, and induced apoptosis. In normal cells, protective mechanisms included reversible microtubule depolymerization and activation of pro-survival signaling via the caspase-8 and riptosome pathways. The therapeutic potential of IBCar was confirmed in mouse models of Luminal B and triple negative BC, where it exhibited strong antitumor activity without detectable toxicity. Conclusions: These findings collectively support IBCar as a promising, effective, and safe therapeutic candidate for breast cancer treatment. Full article

The separation of three proton pump inhibitors (omeprazole, lansoprazole, and rabeprazole) as exemplified molecules containing chiral sulfoxide groups was investigated in polar organic liquid chromatographic mode on seven different polysaccharide stationary phases (Chiralcel OD and OJ; Chiralpak AD, AS, and IA; Lux Cellulose-2 and -4). Different alcohols, such as methanol, ethanol, 1-propanol, 2-propanol, and their combinations, were used as eluents. After method optimization, semi-preparative enantioseparation was successfully applied for the three proton pump inhibitors to collect the individual enantiomers. A detailed investigation was conducted into elution order reversal, thermodynamic parameters, the effect of eluent mixtures, and the hysteresis of retention time and selectivity. Using Chiralpak AS, containing the amylose tris[(S)-α-methylbenzylcarbamate] chiral selector, the separation of the investigated enantiomers was achieved in all four neat eluents, with methanol providing the best results. In many cases, a reversal of the enantiomer elution order was observed. In addition to chiral-selector-dependent reversal, eluent-dependent reversal was also observed. Notably, even replacing methanol with ethanol altered the enantiomer elution order. Both enthalpy- and entropy-controlled enantioseparation were also observed in several cases; however, temperature-dependent elution order reversal was not. The hysteresis of retention and selectivity was further investigated on amylose-type columns in methanol–2-propanol and methanol–ethanol eluent mixtures. The phenomenon was observed on all amylose columns regardless of the eluent mixtures employed. Hystereticity ratios were calculated and used to compare the hysteresis behaviors of different systems. Multivariate statistical analysis revealed that Chiralpak AS exhibited the most distinct enantioselective behavior among the tested columns, likely due to the absence of a direct connection between the carbamate moiety and the aromatic substituent. The present study aided in understanding the mechanisms leading to enantiomer recognition, which is crucial for developing new chiral stationary phases and chiral HPLC method development in general. Full article

Heterocycles—cyclic compounds containing at least one non-carbon heteroatom (e.g., N, O, S)—are fundamental in medicinal chemistry due to their influence on a drug’s physicochemical and biological properties. They improve solubility, bioavailability, and facilitate molecular recognition through their electronic and hydrogen-bonding features. These properties make them indispensable in drug design. This study focuses on the synthesis of a key heterocyclic intermediate: benzyl-N-[4-(2-hydroxyethyl)-1,3-thiazol-2-yl]carbamate. This molecule incorporates a thiazole ring, known for its rigidity and electronic properties, that enhances target interactions. The 2-position bears a Cbz-protected amine, enabling orthogonal deprotection, while the 4-position features a hydroxyethyl side chain, providing a handle for further chemical modifications via nucleophilic substitution. Herein, we report the successful synthesis of this intermediate along with its full ¹H and ¹³C NMR spectra, melting point, and crystal structure, confirming its identity and purity. Full article

Tomatoes are among the most widely consumed and economically significant fruits in the world. However, the extensive use of pesticides in their cultivation has led to the contamination of the peels, posing potential health risks to consumers. As one of the top global producers, consumers, and exporters of tomatoes, Mexico requires rapid, non-destructive, and real-time methods for pesticide monitoring. In this study, a detailed characterization of six pesticides using Raman and Fourier Transform Infrared (FT-IR) spectroscopies was carried out to identify their characteristic vibrational modes. The pesticides examined included different chemical classes commonly used in tomato cultivation: organophosphorus (dichlorvos and methamidophos), pyrethroids (lambda-cyhalothrin and cypermethrin), and carbamates (methomyl and benomyl). Tomato peel samples were examined both before and after pesticide application. Prior to treatment, the peel exhibited a well-organized polygonal structure and showed the presence of carotenoid compounds. After pesticide application, no visible structural damage was observed; however, distinct vibrational bands enabled the detection of each pesticide. Organophosphorus pesticides could be identified through vibrational bands associated with P-O and C-S bonds. Pyrethroid detection was facilitated by benzene ring breathing modes and C=C stretching vibrations, while carbamates were identified through C-N stretching contributions. Phytotoxicity testing in the presence of pesticides indicates no significant damage during the germination of tomatoes. Full article

The relationship between protein structure and function is intrinsically interconnected, as the structure of a protein directly determines its functional properties. To investigate the effects of temperature and pressure on protein function, this study employed ethyl carbamate (EC) hydrolase as a model food enzyme and conducted molecular dynamics (MD) simulations under varying temperature and pressure levels to elucidate its structure–function relationship. By systematically analyzing the dynamic changes in root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), hydrogen bonding, catalytic pocket conformation, and packing density under different temperature and pressure conditions, we revealed the structural adaptability of EC hydrolase. Furthermore, we analyzed the characteristics of EC hydrolase using molecular dynamics simulations with temperature and pressure levels, as well as conformational bias-based computer-aided engineering, providing both theoretical and experimental foundation for the adaptability mechanisms of enzymes under extreme conditions. Full article

We present a protocol for the facile conversion of linear alkenyl N-alkoxy carbamates into cyclic bromo carbonates. The reaction is operationally simple, uses widely available, inexpensive reagents, and requires no rigorous exclusion of air or moisture. A range of functional groups is compatible, and the reaction diastereoselectivities vary from good to excellent. The reactions are scalable, and the resultant carbonates can be further transformed. Full article

This manuscript reports the synthesis and characterization of 19 novel heterostilbene carbamates, designed as selective butyrylcholinesterase (BChE) inhibitors with potential applications in the treatment of neurodegenerative disorders, particularly Alzheimer’s disease. The compounds were synthesized from resveratrol analogs, and their structures were confirmed by NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction for selected derivatives (compounds 1 and 4). In vitro assays demonstrated high selectivity toward BChE over acetylcholinesterase (AChE), with compound 16 exhibiting exceptional inhibitory activity (IC₅₀ = 26.5 nM). Furthermore, compound 16 showed moderate anti-inflammatory effects by inhibiting LPS-stimulated TNF-α production in peripheral blood mononuclear cells. In silico ADME(T) profiling revealed favorable pharmacokinetic properties and low mutagenic potential for the majority of compounds. Molecular docking and molecular dynamics simulations confirmed stable binding interactions within the BChE active site. These results highlight heterostilbene carbamates as promising lead structures for developing novel therapeutic agents targeting neurodegenerative diseases. Full article

In Romania, groundwater is an important source of drinking water, especially in rural areas. This study investigated the concentrations of organophosphorus, carbamate, and triazine pesticides (OPs) along with organochlorine pesticides (OCPs) in groundwater samples collected from the Titu-Sarata Plain. Sensitive analytical techniques were employed, including Ultrahigh-Performance Liquid Chromatography coupled with Q Exactive™ HF Hybrid Quadrupole-Orbitrap™ Mass Spectrometry (UHPLC-Orbitrap-MS/MS) and Gas Chromatography coupled with an electron capture detector (GC-ECD). Environmental and human health risks were assessed in the case of pesticides that exceeded the maximum allowed concentration. The environmental risk assessment (ERA) revealed significant risks associated with Phosdrin, Phorate, and pp’DDE. Additionally, particular concerns arose from the presence of Aldrin and Dieldrin, which pose a high carcinogenic risk, especially through groundwater consumption in agricultural areas. The results of this research highlight the need for the implementation of a continuous quality monitoring program for groundwater in the agricultural regions that were studied. Full article

Background: Indoor residual spraying (IRS) is a core insecticide-based vector control tool employed in most malaria-affected settings globally. However, mosquito vectors have developed resistance to nearly all of the insecticides currently used in IRS. This has necessitated a transition to new classes of insecticides, from mostly using dichlorodiphenyltrichloroethane (DDT) and pyrethroids from 1997 to 2010 to carbamates in 2011 and organophosphates in 2013. In addition, other vector control measures, like the use of long-lasting insecticide-treated bed nets (LLINs), have also been employed for malaria control. Despite the implementation of these mosquito vector control interventions, malaria remains a disease of public health concern, especially in sub-Saharan Africa, which bears over 90% of the disease burden. This review will thus collate evidence on the effectiveness of IRS for malaria control in sub-Saharan Africa. Methods and analysis: The systematic review will be conducted following a priori criteria developed using the PRISMA guidelines. Articles will be obtained through a search of the Web of Science, Google Scholar, Medline via PubMed, Scopus and Embase databases. Mesh terms and Boolean operators (“AND”, “OR”) will be used in the article search. Additionally, websites of malaria research institutions will be searched. The article search will be conducted by two independent librarians (AAK and RS). All identified articles will be transferred to EPPI-reviewer v6.15.1.0 software. Article screening and data abstraction will be performed in duplicate by four reviewers (KOO, LN, GK and MO), and any further disagreements will be resolved through discussion and consensus. We shall extract data on the country, region, study design, insecticide combination, season, susceptibility procedure used, vector control interventions, population, mosquito species, malaria incidence or prevalence, insecticide efficacy, susceptibility, genotypic resistance, vector mortality and knockdown effect. Data analysis will be performed using STATA v17.0. Effect sizes will be statistically pooled using inverse-variance-weighted random-effects meta-analysis. Heterogeneity and publication bias in the articles will be assessed using the I² statistic and a funnel plot, respectively. For the studies that will not be included in the meta-analysis, a narrative synthesis will be written following the Cochrane Consumer and Communication Review Group format. Results: The findings of this review will help generate evidence on the effectiveness of indoor residual spraying using WHO pre-qualified insecticides in malaria control in sub-Saharan Africa. This protocol was registered in PROSPERO, registration number CRD42024517119. Full article

In this study, we assessed the ability of 2-Cl-MGV-1 (2-chlorophenyl quinazolin-4-yl, dimethyl carbamate), a ligand of the 18 kDa mitochondrial translocator protein (TSPO), to mitigate brain damage in a mouse model of traumatic brain injury (TBI). TSPO is important for arresting the death of neurons and glia and counteracting microglial activation, and it provides anti-inflammatory activity, promotes regeneration (including neurons), and contributes to angiogenesis. We assessed the minimal dose of the TSPO ligand 2-Cl-MGV-1 that attenuates the magnitude of brain damage as well as the time window following TBI in which the treatment is effective. We found that 7.5 mg/kg of 2-Cl-MGV-1 can reduce the impact of the TBI as assessed by magnetic resonance imaging (MRI). We also found that 2-Cl-MGV-1 improved motor performance as observed in a treadmill test (80.9% fewer shocks needed and 40.7% more distance covered, both p < 0.05), and reduced anatomical brain damage (by 86.5%, p < 0.05), cell death (by 75.0%, p < 0.001), and microglial inflammatory response (by 50.2%, p < 0.01). The treatment also increased expression of neuronal markers NeuN and β3-tubulin (30.0%, p < 0.01; 36.0%, p < 0.01, respectively). The time window in which we found the treatment to be effective was 3–11 h after TBI. Our study suggests that agents active at the TSPO can significantly attenuate the outcome of TBI, including in the structural, cellular, and neuro-behavioral dimensions. The mechanisms involved in the attenuation of brain damage following TBI may be related to a decrease in cell death and to anti-inflammatory activity. TSPO seems to be a novel target for the development of agents aimed at the suppression of neurodegenerative processes. Full article

Aquaculture has been rapidly growing during the past decade to accommodate the increasing need for seafood as a vital source of nutrients for human beings. The nutritional benefits of incorporating fish into one’s diet are paramount in promoting overall health, bolstering immunity and warding off diseases. Nonetheless, farm-raised aquatic species are frequently subjected to elevated contamination levels due to pesticides, antibiotics, and heavy metals in the marine environment. Pesticides affect fish differently based on species, class, dosage, and exposure duration. They can induce histological damage or neurobehavioral changes by inhibiting acetylcholinesterase production. This can promote liver dysfunction, metabolism deregulation, oxidative stress, and hematological imbalances, impair immune responses, and adversely affect fish reproduction. Furthermore, pesticides negatively affect the nutritional composition of fish by reducing the total protein levels in muscle, liver, gills, and kidney tissues. They disrupt lipid metabolism, resulting in lipid accumulation in the liver and a decrease in polyunsaturated fatty acids. Additionally, pesticides interfere with metabolism by altering carbohydrate levels in the gills, muscles, and kidneys while decreasing glycogen storage in the liver. Pesticide exposure has been linked to severe health impacts in humans, such as non-communicable diseases, reproductive issues, cognitive dysfunction, and cancer. The current review comprehensively emphasizes the harmful effects of pesticides on fish and human health, urging the establishment of environmental monitoring programs and biomonitoring studies. It accentuates the need for risk assessment models to evaluate pesticide impacts on marine ecosystems and advocates for stricter safety standards and lower pesticide residue limits in aquaculture products. Full article

The relationship between various central nervous system (CNS) disorders linked to pesticide exposure highlights a growing concern worldwide, as the extensive use of these compounds causes toxic effects on the CNS of non-target organisms. Reports indicate that exposure to pesticides, including carbamates, organophosphates, and pyrethroids, produces various adverse impacts on neurological function in humans, ranging from acute symptoms such as headaches and dizziness to long-term conditions leading to developmental delays in children, cognitive impairment, and neurodegenerative diseases, such as Parkinson’s and Alzheimer’s being among the most important. The scientific evidence suggests that pesticide exposure induces oxidative stress and disruptions in neurotransmission, resulting in neuronal damage and alterations in brain development. The review discusses scientific evidence of neurodegenerative disease development related to pesticide exposure, as well as alternatives to chemical pesticides used in agriculture, emphasizing Agroecological Crop Protection (ACP), which combines biological control, crop rotation, and natural predators and is presented as a practical approach to reducing reliance on pesticides. Organic farming methods, which employ natural substances and minimal input of chemicals, also offer safer alternatives. In addition, advances in biopesticides, which target specific pests without harming non-target organisms, provide promising solutions that protect the environment and human health. Pesticides are well-known environmental stressors that menace biodiversity and pose important threats to human health. Reducing pesticide use and remediating pesticide-polluted sites are urgent tasks to avoid adverse effects of pesticide exposure in non-target organisms. Full article

Currently, the most promising alternative to the use of the phosgenation reaction, for large-scale production of isocyanates, ureas, and carbamates, appears to be the Pd-catalyzed oxidative carbonylation of arylamines. During the reaction, the Pd(II) catalytic species are reduced to Pd(0) and the addition of sacrificial oxidizing agents is usually necessary to restart the catalytic cycle. Among these oxidizing agents, molecular oxygen is undoubtedly the more appealing, from an economical and green point of view, but it is not so efficient, whereas several metal salts (named cocatalysts) can be used, able to form redox couples with Pd(0) or to act as electron transfer mediators with oxygen itself. Testing several Pd(II) complexes, metal cocatalysts, and promoters, we have found that the [PdCl₂(dppf)]/FeCl₃/LiBr = 1/1200/200 (mol/mol) system efficiently catalyzes the carbonylation of aniline to form 1,3–diphenylurea selectively (100%) with a TOF of ca. 1177 h⁻¹. On the other hand, the addition of oxygen to such a system strongly increases the aniline conversion (0.3 MPa of O₂ increases the TOF at ca. 3930 h⁻¹), but it moves the selectivity towards the phenyl isocyanate (65%, mol/mol). Full article

CO₂, an abundant and renewable C1 source, presents significant potential for applications in organic synthesis. Hydrazones, recognized for their distinctive properties, exhibit high versatility in synthetic chemistry, facilitating numerous chemical transformations. Given their crucial roles in organic synthesis, the combination of CO₂ with hydrazones has garnered increasing research interest. This review provides a comprehensive summary of recent progress in reactions involving CO₂ and hydrazones or their derivatives. These include the coupling of amines and N-tosylhydrazones with CO₂, the umpolung-mediated carboxylation of hydrazones/N-tosylhydrazones with CO₂, the cyclization of hydrazones with CO₂, and lactamization reactions incorporating N-tosylhydrazones and CO₂. These transformations utilize the diverse reactivity of hydrazones and their derivatives to capture and convert CO₂, generating valuable organic compounds with both academic and practical relevance. Additionally, the review examines the mechanisms underlying these reactions, offering critical insights for advancing research in this area. Full article

The formation of (R)-methyl-(2-hydroxy-1-phenylethyl)carbamate through Pd(PPh₃)₄-catalyzed synthesis was investigated using computational methods to elucidate the reaction pathway and energetic feasibility. Density functional theory (DFT) calculations confirmed that the direct reaction between (R)-(-)-2-phenylglycinol and methyl chloroformate is not spontaneous, requiring a catalyst to proceed efficiently. The study proposes a detailed mechanistic pathway involving ligand dissociation, intermediate formation, and hydrogenation. The role of Pd(PPh₃)₄ was examined, demonstrating its ability to stabilize reaction intermediates and facilitate key transformations, such as dehydrogenation and chlorine elimination. Two reaction pathways were identified, with Pathway 1 exhibiting a net energy of –84.7 kcal/mol and Pathway 2 showing an initial positive energy of 90.1 kcal/mol. However, the regeneration of key intermediates in Pathway 2 ultimately reduces the total reaction energy to –238.7 kcal/mol, confirming the feasibility of both routes. Computational results align with experimental NMR data, supporting the formation of the proposed intermediates. These findings provide valuable insights into catalyst optimization, suggesting that ligand modifications or alternative palladium-based catalysts could enhance efficiency. This study advances the understanding of Pd-catalyzed carbamate synthesis and offers a basis for future experimental and computational investigations. Full article