Search Results (303)

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a major heat-induced contaminant in protein-rich foods, yet its effects on intestinal barrier homeostasis and luminal microecology remain insufficiently defined. In this study, adult zebrafish were exposed to dietary PhIP for 90 days at estimated intake doses of 0.006, 0.4, and 7.2 mg/kg bw/day to evaluate intestinal injury, microbial dysbiosis, and metabolic remodeling. PhIP exposure impaired growth-related indices and induced progressive intestinal lesions, accompanied by mucus barrier depletion, reduced goblet cell abundance, and downregulation of muc2. Tight junction integrity was disrupted, as indicated by decreased zo-1, occludin, and claudin1 expression, weakened ZO-1 and Claudin-1 immunofluorescence signals, and reduced tight junction-related protein levels. Serum LPS and intestinal pro-inflammatory cytokines were markedly elevated, whereas il-10 expression was suppressed, indicating increased endotoxin burden and inflammatory activation. 16S rRNA gene sequencing revealed Proteobacteria-enriched dysbiosis and exposure-associated shifts in candidate genera, including Chitinilyticum, Shewanella, Aeromonas, Acinetobacter, Microbacterium, and Reyranella. Untargeted metabolomics further identified luminal metabolic remodeling involving lipid-related compounds, organic acids, amino acid metabolism, arachidonic acid metabolism, the citrate cycle, and pathways related to choline and glycerophospholipid metabolism. Association analysis linked genus-level microbial variation and core pathway-related metabolites with LPS, inflammatory cytokines, and tight junction markers. These findings indicate that dietary PhIP exposure disrupts intestinal barrier homeostasis in parallel with Proteobacteria-related dysbiosis and luminal metabolic remodeling, providing an integrated microbiota-metabolite-barrier association framework for evaluating intestinal risks of heat-induced food contaminants. Full article

Imidazolidin-2-thiones are versatile sulfur-containing heterocycles with broad biological relevance. The synthesis of (3aR,7aR)-1,3-bis(4-aminobenzyl)octahydro-2H-benzo[d]imidazole-2-thione (an imidazolidin-2-thione derivative) from trans-(R, R)-diaminocyclohexane is presented via a three-step sequence: formation of a Schiff base from 1,2-diamine and 4-nitrobenzaldehyde, followed by reduction with NaBH₄; thiocarbonylation under microwave irradiation (MW) to generate the imidazolidin-2-thione core; and reduction of the nitro substituents to amines using an iron/CaCl₂ system. The structure of the final compound was confirmed by detailed ¹H and ¹³C NMR analyses, demonstrating the preservation of the bicyclic backbone and the successful conversion of the nitro functional group. The overall yield of the sequence was 28%, with the reduction of the nitro group identified as the rate-limiting step. This protocol represents a viable synthetic strategy for obtaining functionalized imidazolidin-2-thiones useful for the development of novel bioactive sulfur-containing heterocycles. Full article

A novel nitrogen-containing heterocyclic compound, 4-(6-Chloropyridin-3-yl)-6-cyclopropylpyrimidin-2-amine, was designed and synthesized using 6-chloropyridin-3-aldehyde and cyclopropyl methyl ketone as starting materials. The structure of the target compound was characterized by ¹H NMR, ¹³C NMR and HRMS, and the spectral data were consistent with the expected structure, confirming the correctness of the product. Full article

Understanding the adsorption mechanisms of anions onto functional monomers is crucial for various applications in environmental remediation and chemical separation. In this study, we investigated the interactions of ReO₄⁻, Cl⁻, SO₄²⁻, and F⁻ with several organic functional monomers featuring aliphatic chains, cyclic saturated or unsaturated rings, and NH/NH₂ functional groups through density functional theory calculations. Employing a rigorous multilevel optimization strategy, we explored the geometric and energetic features of their complexes, focusing on hydrogen bonding and anion–heterocycle interactions. Our results highlight the strong affinity of ReO₄⁻, Cl⁻, SO₄²⁻ for amine-type functional monomers, while also revealing the distinct interaction patterns of F⁻ with aromatic rings containing nitrogen. This comprehensive analysis elucidates diverse binding mechanisms, providing insights into designing effective adsorbents for selective anion capture. Full article

Di(hetero) aryl and alicyclic amine derivatives of thieno[2,3-b]pyridine were synthesized in good to high yields (45–76%) via palladium-catalyzed Buchwald–Hartwig amination. The reactions were performed using methyl 5-bromothieno[2,3-b]pyridine-2-carboxylate, prepared in this work, and a variety of substituted anilines bearing either electron-donating groups (EDGs) or electron-withdrawing groups (EWGs), as well as pyridinyl amines, and saturated heterocyclic amines such as morpholine and piperidine. For most substrates, the optimal conditions involved Pd(OAc)₂, rac-BINAP, and Cs₂CO₃ in toluene at 100 °C under argon. Substrate bearing EWGs and electron-deficient pyridinyl amines required Xantphos as the ligand, while reactions with piperidine were only successful using Pd₂(dba)₃ as a palladium (0) source. The antiparasitic activity of the synthesized compounds was evaluated against Trypanosoma brucei (T. brucei) and Leishmania infantum (L. infantum) in both promastigote and amastigote forms. Most compounds exhibited no significant cytotoxicity (CC₅₀ > 100 μM) in PMA-differentiated THP-1 derived macrophage cells. Analysis of substituent effects focusing on the nature of amino substitution at position C(5) revealed distinct trends in antiparasitic activity. Notably, one compound exhibited activity against Leishmania infantum promastigotes that was nearly four times higher than that of the reference drug miltefosine, and its selectivity index was also approximately fourfold higher. Full article

Pyrrolo[2,3-d]pyrimidine is a privileged fused heterocyclic scaffold that has attracted considerable attention in medicinal chemistry due to its diverse biological activities. Herein, we report an efficient synthesis strategy for the preparation of the pyrrolo[2,3-d]pyrimidine-based natural toyocamycin aglycone and pyrrolo[2,3-d]pyrimidine derivatives. The synthesis of toyocamycin aglycone features a key benzylamine nucleophilic substitution followed by a palladium-catalyzed cyanation reaction. From a key intermediate derived from this route, nineteen new pyrrolo[2,3-d]pyrimidine derivatives were rapidly synthesized via key Suzuki–Miyaura coupling and amine nucleophilic substitution reactions. Their cytotoxic activities were evaluated against Huh-7 and HepG liver cancer cell lines. Most derivatives were inactive after 24 h. However, 28a–28c, 28e and 28f exhibited moderate cytotoxicity with IC₅₀ values ranging from 5.7 to 62.6 μM. Among them, compound 28e displayed the highest potency against HepG cells, with IC₅₀ values of 5.7 μM. Compared with normal HEK293 cells, it showed a selectivity index (SI) of 3.60 against HepG cells. Preliminary structure-activity relationship analysis suggested that incorporation of a cyclopropyl group further improves antitumor activity. Full article

Gold(I) complexes are particularly useful as catalysts in a variety of reactions including, in particular, the electrophilic activation of alkyne substrates, yet they generally require the addition of a silver salt to activate the gold complex by removing an anionic ligand. This results into higher costs and possible problems related to the non-innocence of the silver additive. In this contribution, we highlight the possibility to proficiently use a dinuclear monocationic gold(I) complex developed in our laboratory as a silver-free catalyst. The complex, featuring a bridging N-phosphanyl-N-heterocyclic carbene (NHCP) ligand, indeed exhibits notable activity and selectivity in standard alkyne hydroamination and hydroalkoxylation reactions, particularly in the case of internal alkynes and secondary aromatic amines as substrates. Full article

Cellular senescence (CSEN) is caused by a variety of factors that trigger complex molecular pathways. These include telomere shortening, oncogene activation and replicative stress, as well as DNA damage caused by genotoxic anticancer drugs and endogenous and exogenous genotoxins. Here, we review the induction of CSEN by exogenous genotoxic insults resulting from food and environmental exposures. The available data show that genotoxins/carcinogens in tobacco smoke and smokeless tobacco, in the environment, in food, beverages and life-style products induce CNS. The exposures include N-nitroso compounds, polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, acrylamide, heavy metals, fine dust, mycotoxins, phytotoxins, and phycotoxins. Also, heme in red meat contributes to CSEN as it catalyzes the formation of genotoxic species in the colon. Induction of CSEN by external genotoxins/carcinogens is bound on the DNA damage response pathway (DDR), which relies on activation of the ATM/ATR-CHK2/CHK1-p53-p21 axis and the p53-independent p16/p14 axis, eliciting cyclin-dependent kinase inhibition and permanent cell cycle arrest. Other factors that can be involved are DREAM, MAPK, cGAS/Sting, and NF-κB. The accumulation of non-repaired DNA damage triggering CSEN following external genotoxic exposures may contribute significantly to the amelioration of senescent cells and organ failure with age in humans. Senescent cells drive, via the senescence-associated secretory phenotype (SASP), inflammation that is involved in many diseases, including cancer. Although most of the studies were performed with in vitro cell systems, the consequences of CSEN induction by genotoxic nutritional components and environmental exposures seem to be underestimated. Since CSEN correlates with aging, it is reasonable to conclude that exogenous genotoxic pollutants contribute significantly to the aging process through CSEN induction. In light of these findings, it is deduced that reducing genotoxin exposures and using “rejuvenation” supplements (senotherapeutics) are reasonable strategies to counteract cellular senescence and the aging process. Full article

In the present work, we describe the synthesis of a new heterocyclic derivative, 2-(naphthalen-1-yl)-2,3,5,6-tetrahydro-1H-isoquinolino[8,1,2-hij]quinazoline 1, using the reaction between the aminal 1,3,6,8-tetraazatricyclo[4.4.1.1^3,8]dodecane 2 (TATD) and 1-naphthylamine 3 as the first scaffold of a four-step linear synthetic route. In the first step, a condensation catalyzed by acetic acid in 96% ethanol was carried out, leading to the formation of the intermediate 3-(naphthalen-1-yl)-1,2,3,4-tetrahydrobenzo[h]quinazoline 4. Subsequently, this intermediate was acylated with 2-chloroacetyl chloride in the presence of triethylamine and under an inert atmosphere, obtaining the compound 2-chloro-1-(3-(naphthalen-1-yl)-3,4-dihydrobenzo[h]quinazolin-1(2H)-yl)ethan-1-one 5. In the third step, an intramolecular Friedel–Crafts cyclization was carried out using aluminum trichloride as a catalyst, yielding 2-(naphthalen-1-yl)-1,2,3,6-tetrahydro-5H-isoquinolino[8,1,2-hij]quinazolin-5-one 6. Finally, the reduction of this lactam with phosphorus pentachloride and sodium borohydride under anhydrous conditions led to the further closure of the polycyclic system, yielding the final product 1. The proposed route demonstrates the feasibility of using TATD 2 as a versatile precursor for constructing condensed heterocyclic systems of structural interest and potential relevance in advanced organic synthesis. Full article

Exogenous toxic compounds in foods, arising from agricultural practices, environmental contamination, industrial processing, and packaging migration, remain a major global concern for food safety. These contaminants include mycotoxins, veterinary drug residues, antibiotics, pesticides, per- and polyfluoroalkyl substances, heterocyclic aromatic amines, and polycyclic aromatic hydrocarbons, which have multiple adverse effects on human and animal health. The continued presence of these substances highlights the need for reliable exposure assessment, strengthened regulatory frameworks, and advanced analytical methodologies. Food matrices introduce variability in analytical performance, making sample preparation a critical and often limiting step. Conventional extraction techniques such as solid-phase extraction, liquid–liquid extraction, and Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) are still widely applied. Moreover, recent advances have highlighted sustainable alternatives aligned with the principles of green analytical chemistry. In this context, this review provides a comprehensive overview of recent advances (2020–2025) in environmentally friendly extraction techniques for determining exogenous toxic compounds in food samples analyzed by liquid chromatography coupled with mass spectrometry (LC–MS), including their sustainability. Special attention is given to the chemical nature and toxicological relevance of major exogenous organic contaminant families (specialized categories such as hormones and packaging-derived bisphenols were excluded due to distinct migration and metabolic pathways; however, these topics exceed the scope of this manuscript), the analytical challenges associated with different food matrices, and the evolution of extraction and cleanup techniques. Overall, this review integrates analytical robustness, matrix effects, and green metrics to support the development of reliable and more sustainable sample preparation strategies. Full article

Three Schiff base fluorescent probes 3a–3c with N-heterocyclic structure were designed and synthesized by using the reaction of 4-diethylaminosalicylaldehyde with different N-heterocyclic amines, such as 2-aminobenzimidazole, 2-aminobenzothiazole, and 2-amino-6-methylpyridine. Compound 3a exhibited excellent selectivity towards Hg²⁺, with a detection limit of 3.21 × 10⁻⁷ M and a response time of only 30 s. It could be used as a fluorescent probe for detecting Hg²⁺. Meanwhile, compounds 3b and 3c exhibited excellent selectivity towards Zn²⁺, with detection limits of 1.61 × 10⁻⁷ M and 2.03 × 10⁻⁷ M, respectively, and response times of only 30 s. They could serve as fluorescent probes for detecting Zn²⁺. Using probe 3a for Hg²⁺ as an example, the detecting mechanism was further elucidated through ¹H NMR, ESI-MS testing, and DFT calculation analysis. For compound 3a, the coordination stoichiometry between compound 3a and Hg²⁺ was verified to be 1:1 through a Job’s plot. After coordination with Hg²⁺, the molecular rigidity of compound 3a was enhanced, which inhibited the non-radiative decay process and led to the closure of the excited-state intramolecular proton transfer (ESIPT) effect. At the same time, the fluorescence intensity was significantly increased through the chelation-enhanced fluorescence (CHEF) mechanism, which was confirmed by density functional theory (DFT) calculations. In addition, compounds 3a–3c were successfully applied in practical water samples and test strips for the detection of Hg²⁺/Zn²⁺. Full article

Heterocyclic sulfur and nitrogen containing compounds capable of forming an equilibrium: thiol/imine = thione/amine (N=C-S-H ⇌ H-N-C=S) were reacted with levoglucosenone (LG) in the presence of triethylamine. Unexpectedly, the only isolated products were the result of the aza-Michael addition. No S-adducts were detected. All products were crystalline with good to excellent yields. The structure of products was determined using NMR, MS, and single-crystal X-ray analysis. Full article

Background: 8-Quinolinol and its derivatives are drawing significant attention across various disciplines due to their remarkable versatility. These compounds are well-known for their exceptional chelating ability, forming stable metal complexes via their nitrogen and oxygen electron donor atoms. This main characteristic determines their broad utility. Biological activity can also be explained by the chelating capacity, which allows 8-quinolinol to bind to essential metal ions such as Fe, Zn, Cu, and others. This chelation disrupts metal-dependent biological processes in target cells or organisms, leading to a range of effects, including antimicrobial, anticancer, antifungal, and neuroprotective activities. On the other hand, the biological activity of pyrazole derivatives is attributed to their heterocyclic structure, which allows for interactions with biological targets that can lead to enzyme inhibition, receptor antagonism, radical scavenging, and other effects. Objective: This work aimed to synthesize and characterize novel diazene compounds derived from 8-quinolinol or 2-methyl-8-quinolinol and pyrazole amines, and to evaluate their antimicrobial and anticancer activities. Methods: The compounds have been synthesized by coupling diazonium salts obtained from the diazotization of heterocyclic amines with 8-quinolinol and its derivative, 2-methyl-8-quinolinol. The careful selection of reaction conditions enabled the synthesis of high-purity products. The compounds were characterized by 1D and 2D NMR, FT-IR spectroscopy, UV-Vis spectroscopy, and LC-HRMS analysis. The biological activity of the newly synthesized compounds was evaluated following the protocols of EU-OPENSCREEN, a European Research Infrastructure Consortium (ERIC) initiative dedicated to supporting early drug discovery. Results: By combining diazonium salts obtained from 3-methyl-1H-pyrazol-5-amine and ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate with the aforementioned coupling agents, four novel 8-quinolinol derivatives were synthesized. The further hydrolysis of the ethoxy carbonyl functional group allowed its conversion to a carboxylic functional group, thus expanding the series of new compounds to six members. Several compounds from the series have proven to be biologically active against several human pathogenic microorganisms and the Hep-G2 cancer cell line. Conclusions: The combination of two well-known biologically active scaffolds through a classic diazo coupling reaction allowed the synthesis of novel biologically active compounds, which showed promising results as possible antifungal and anticancer agents. These results represent a foundation for future studies, which will include a broader biological screening and in vivo studies. Full article

Molecularly Imprinted Polymer (MIP)-based sensors have gained increasing attention in the field of food safety analysis due to their unique ability to selectively recognize and quantify chemical contaminants and allergens with interesting sensitivity. These synthetic receptors, often referred to as “plastic antibodies,” offer several advantages over conventional analytical methods, including high stability, cost-effectiveness, reusability, and compatibility with miniaturized sensor platforms. This review provides a comprehensive overview of recent advances in the design, fabrication, and application of MIP-based sensors for the detection of a broad range of food contaminants, including pesticides, antibiotics, mycotoxins, heavy metals, acrylamide, heterocyclic amines, allergens, viruses, and bacteria. Various transduction mechanisms—electrochemical, optical, thermal, and mass-sensitive—are discussed in relation to their integration with MIP recognition elements. The review also highlights the advantages and limitations of MIPs in comparison with traditional techniques such as ELISA and HPLC. Finally, we explore current challenges and emerging trends, including nanomaterial integration, multiplexed detection, and smartphone-based platforms, which are expected to drive future developments toward real-time, point-of-need, and regulatory-compliant food safety monitoring tools. Full article