Search Results (212)

In this study, a series of novel β-phenylalanine derivatives were synthesised and evaluated for their anticancer activity. The 3-(4-methylbenzene-1-sulfonamido)-3-phenylpropanoic acid (2) was prepared using β-phenylalanine as a core scaffold. The β-amino acid derivative 2 was converted to the corresponding hydrazide 4, which enabled the development of structurally diverse heterocyclic derivatives including pyrrole 5, pyrazole 6, thiadiazole 8, oxadiazole 11, triazoles 9 and 12 with Schiff base analogues 13 and series1,2,4-triazolo [3,4-b][1,3,4]thiadiazines 14. These modifications were designed to enhance chemical stability, solubility, and biological activity. All compounds were initially screened for cytotoxicity against the A549 human lung adenocarcinoma cell line, identifying N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxo-1-phenylpropyl]-4-methylbenzenesulfonamide (5) and (E)-N-{2-[4-[(4-chlorobenzylidene)amino]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1-phenylethyl}-4-methylbenzenesulfonamide (13b) as the most active. The two lead candidates were further evaluated in H69 and H69AR small cell lung cancer lines to assess activity in drug-sensitive and multidrug-resistant models. Schiff base 13b containing a 4-chlorophenyl moiety, retained potent antiproliferative activity in both H69 and H69AR cells, comparable to cisplatin, while compound 5 lost efficacy in the resistant phenotype. These findings suggest Schiff base derivative 13b may overcome drug resistance mechanisms, a limitation commonly encountered with standard chemotherapeutics such as doxorubicin. These results demonstrate the potential role of β-phenylalanine derivatives, azole-containing sulphonamides, as promising scaffolds for the development of novel anticancer agents, particularly in the context of lung cancer and drug-resistant tumours. Full article

In this study, a C-C bond-linked triazole-fused oxadiazole energetic compound, 4-amino-5-(4-amino-1,2,5-oxadiazol-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1), was successfully designed and efficiently synthesized. Following nitration, a functional group-modified nitramine energetic compound (2) was obtained, and its energetic ionic salt (3) was further prepared. A comprehensive characterization of the structures of these three compounds was conducted, resulting in the successful elucidation of the single-crystal structures of compound 2·Ca²⁺·6H₂O and compound 3·MeOH. Compound 2 exhibited a positive formation enthalpy (56.2 kJ·mol⁻¹) and moderate mechanical sensitivity (FS = 120 N, IS = 12 J). Due to the presence of the nitramine group, compound 2 exhibited a relatively low thermal decomposition temperature (T_dec = 94 °C). However, the thermal stability of compound 3 was significantly improved (T_dec = 233 °C), which is attributed to salt formation. Compound 3 exhibits a positive formation enthalpy (121.0 kJ·mol⁻¹), along with excellent detonation performance (D = 8120 m·s⁻¹, P = 32.1 GPa) and reduced mechanical sensitivity (FS = 224 N, IS = 24 J). Therefore, the multi-heterocyclic compound, joined via C-C bond linkage, demonstrates outstanding performance, offering a new avenue for the design and synthesis of energetic materials. Full article

Compounds containing the pentazolate anion (cyclo-N₅⁻) represent a distinctive group of energetic materials that have received extensive attention in recent years. Cyclo-N₅⁻ was used as a polynitrogen anion for the syntheses of energetic salts through metathesis reactions. Propamidinium (1), 5-amino-4-carbamoyl-1H-imidazol-3-ium (2), (1H-1,2,3-triazol-4-yl)methanaminium (3), 5-amino-4H-1,2,4-triazol-1-ium (4), 5-amino-3-methyl-4H-1,2,4-triazol-1-ium (5), and amino(pyrimidin-2-yl)methaniminium (6) pentazolates were obtained with high yields (>80%), and their crystal structures were confirmed through single-crystal X-ray diffraction analyses. Hirshfeld surface analyses and 2D fingerprint plots generated by CrystalExplorer17 demonstrated that these compounds exhibited extensive hydrogen-bonding networks in their crystal packing. Mechanical sensitivity tests showed that all the prepared salts were highly insensitive (IS > 35 J, FS > 360 N), providing valuable insights for the further exploration of broader energetic materials containing cyclo-N₅⁻. Full article

The synthesis of a new acyclic and cyclic series of D-Ala-AMP analogues was reported. Chemical modifications were introduced on the carbohydrate, the sulfamate linker, and/or the amino-acid N-terminal moiety in order to increase in vivo stability and cell permeability. These new compounds were evaluated in vitro as DltA inhibitors and also in vivo as adjuvant antibiotics to re-sensitize methicillin-resistant Staphylococcus aureus. Indeed, we showed that seven nucleosides containing either a fluorine atom, an azido group, a difluorophosphonylated allylic ether moiety onto the 2′-position, or a sulfamate and a triazole as the sulfamate linker had moderate to excellent IC₅₀ values. Among all these new DltA inhibitors, two molecules functionalized by the fluorinated ether or the sulfamide linker were able to efficiently re-sensitize MRSA to imipenem. Quantification of D-alanyl esters confirmed that these two compounds reduced the level of bacterial cell wall D-alanyl residues by 50% and 80%. Full article

Oxidative stress plays a critical role in regulating sperm function, yet species-specific antioxidant mechanisms remain poorly understood. This study compared hydrogen peroxide (H₂O₂) tolerance in horse and human sperm and investigated the roles of catalase and glutathione peroxidase (GPx) in horses. A H₂O₂ dose–response assay (0–2000 µM) showed that horse sperm were significantly more resistant to oxidative damage, with an IC₅₀ for progressive motility over 14-fold higher than that of human sperm (391.6 µM vs. 27.3 µM). Horse sperm also accumulated more intracellular H₂O₂ without loss of motility or viability. DNA damage assays (Halo and SCSA) revealed H₂O₂-induced fragmentation in human but not horse sperm. Enzyme inhibition experiments in horse sperm using 3-amino-1,2,4-triazole (catalase inhibitor) and (1S,3R)-RSL3 (GPx inhibitor) at 250 µM H₂O₂ showed that catalase inhibition severely impaired motility and increased intracellular H₂O₂ > 100-fold, while GPx inhibition had a milder effect (~5-fold increase). Immunocytochemistry localized catalase to the sperm head, particularly the post-acrosomal region, challenging the notion that sperm lack peroxisomes. The dependence of horse sperm on oxidative phosphorylation may drive the need for enhanced antioxidant defenses. These findings reveal species-specific oxidative stress adaptations and highlight catalase as a key antioxidant in equine sperm. Full article

HIV/AIDS and Mycobacterial tuberculosis (Mtb) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate to good yields. Compounds 11g (IC₅₀ = 0.388 µM), 11h (IC₅₀ = 0.01032 µM) and 11i (IC₅₀ = 0.167 µM) exhibited the most promising in vitro activities against the wild-type HIV-1 subtype B, with 11h being 9-fold more active than AZT (IC₅₀ = 0.0909 µM), the reference drug. Furthermore, compound 11h displayed moderate activity, with a MIC₉₀ of 88μM against Mtb’s H37Rv strain. Cytotoxicity studies on TZM-bl cell lines revealed that most of the tested compounds were generally non-cytotoxic; the selectivity index (SI) for 11h, the front runner, is >2472. Molecular docking studies revealed that 11h interacted with Phe112, Tyr108, Glu283 and Trp86 amino acid residues in the active site of HIV-1. DFT studies revealed that 11h has the ability to donate and accept electrons to and from available orbitals. The predicted ADMET studies showed that these compounds possess drug-likeness, and 11h has the potential for further optimisation as an anti-HIV-1 agent. Full article

A novel 3-amino-5-mercapto-1,2,4-triazole functionalized graphene oxide composite (GO-ATT) was successfully prepared via a covalent coupling method, then employed for the removal of p-nitrophenol (PNP) from wastewater. The morphology as well as the composition of GO-ATT composite were investigated using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction spectroscopy (XRD), and X-ray photoelectron spectroscopy (XPS). The surface charge of GO-ATT composite was evaluated by Zeta potential analyses. The surface area and pore size distribution of GO-ATT composite were analyzed using specific surface analyses using the Brunauer–Emmett–Teller (BET) method. Batch adsorption experiments were performed to investigate the effects of conditional factors, including contact time, solution pH, initial PNP concentration, and contact temperature, on the adsorption process. A maximum adsorption capacity of PNP by GO-ATT composite (0.287 mmol g⁻¹) could be obtained at 25 °C. Freundlich isotherm (R² > 0.92505) can better describe the adsorption behavior of PNP on GO-ATT composite. The thermodynamic functions (ΔG°, ΔH°, ΔS°) indicate that adsorption is a spontaneous, endothermic, entropy-increasing process and features physisorption. The adsorption behavior of PNP on GO-ATT composite conformed to the nonlinear pseudo-second-order kinetic model. Adsorption mechanism investigation indicated that the electrostatic, π-π stacking, and hydrogen bonding interactions were involved in the adsorption process. After 10 adsorption–desorption cycles, the adsorbent exhibited a stable and efficient removal rate (94%) for PNP. Due to its advantages of a high efficiency, excellent reusability, and high stability, the covalently coupled GO-ATT composite might be used as an effective adsorbent for the removal of phenolic contaminants from wastewater. Full article

Nitrogen-containing substitutes, such as 1,2,3-triazoles and Mannich bases, are major pharmacophore systems, among others. The presented review summarizes the recent advances (2019–2024) in the synthesis of 1,2,3-triazoles and Mannich bases conjugated with a triterpenic core. These structural modifications have proven to be effective strategies for modulating the biological activity of triterpenes, with particular emphasis on antitumor and antiviral properties. Recent efforts in expanding the structural diversity of triazoles through A-ring modifications and C28 (or C30) substitutions are discussed. Notably, the first examples of N-alkylation of indole triterpenoids by propargyl bromide are presented, along with the application of propargylamine in the synthesis of rare triterpenic aldimines. The review also covers an application of triterpene alkynes in Mannich base synthesis, focusing on functionalization at various positions, including C28 and C19 of the lupane platform, and incorporating of amino acid spacers. While significant progress has been made both in synthetic strategies and pharmacological applications, further research is needed to fully explore the antibacterial, anti-inflammatory, and antidiabetic potential. The review will be useful to researchers in the fields of organic synthesis, natural product and medicinal chemistry, and pharmacology. Full article

Triazoles are important fragments in the development of fungicidal compounds. Fungi have gradually developed drug resistance against traditional fungicides due to long-term overuse. Therefore, there is an urgent need to discover new candidate compounds. A series of 1,2,4-triazole derivatives containing amino acid fragments were designed and synthesized based on mefentrifluconazole. All the target compounds were characterized by ¹H-NMR, ¹³C-NMR, and HRMS techniques. Their antifungal activities against five kinds of phytopathogenic fungi were evaluated in vitro. The results revealed that most compounds had broad-spectrum fungicidal activities at 50 μg/mL and four compounds exhibited better antifungal activity than the control drug mefentrifluconazole. Interestingly, the synthesized compounds 8d and 8k exhibited exceptional antifungal activity against Physalospora piricola, with EC₅₀ values of 10.808 µg/mL and 10.126 µg/mL, respectively. Molecular docking studies demonstrate that the 1,2,4-triazole derivatives 8d and 8k, which incorporate amino acid groups, exhibit strong binding affinity to 14α-demethylase (CYP51). These findings highlight the potential of these compounds as effective antifungal agents. Full article

As examples of “Click Chemistry”, the reaction of 1-(oxiran-2-ylmethyl)piperidine with several 1,2,4-triazoles derivatives was studied. As a result, the reaction shows that the oxirane ring opens regiospecifically, according to Krasusky’s rule, without using a catalyst. The basic nitrogen present in 1-(oxiran-2-ylmethyl)piperidine has a catalytic (anchimer) effect. Full article

An efficient access to novel 2-substituted 1H-imidazole derivatives was developed based on acid-mediated denitrogenative transformation of 5-amino-1,2,3-triazole derivatives available through dipolar azide−nitrile cycloaddition (DCR). The proposed approach includes intramolecular cyclization of 5-amino-4-aryl-1-(2,2-diethoxyethyl) 1,2,3-triazoles followed by triazole ring opening and insertion of in situ formed carbene intermediate into the O-H bond of different alcohols under acidic conditions. Full article

Experimental protocols based on Electron Paramagnetic Resonance (EPR) and Raman spectroscopy are presented for the investigation of the Fe(II) spin transition in Cu(II)-doped 1-D spin-crossover (SCO) nanoparticles of the type [Fe_1−xCu_x(NH₂trz)₃]Br₂ where x = 0.03 and 0.06 and NH₂trz = 4-amino-1, 2, 4-triazole. The resulting nanoparticles were characterized using Transmission Electron Microscopy (TEM), Infrared (IR) spectroscopy, and powder X-ray diffraction (p-XRD). Magnetic susceptibility measurements revealed a dependence on the scan rate, with critical temperatures and hysteresis widths varying accordingly. EPR spectroscopy provided insights into the doped nanoparticles’ structural changes and spin-state transitions. The Cu(II) dopants exhibited significant g-factor anisotropy and hyperfine structure, indicative of a distorted octahedral coordination. The EPR spectra indicated that the spin transition occurs in domains populated by ions of the same spin state. Cu(II) ions show different spectral characteristics depending on whether they are in high-spin or low-spin domains of Fe(II). Changes in Raman bands induced by laser power reveal structural and electronic rearrangements during the LS to HS transition. The findings provide insights into metal–ligand interactions and the molecular mechanisms underlying the SCO process. Full article

The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM). Single and three-day administration of TPY3m (i.p., 20 mg/kg) was studied, and the effect of TPY3m on the HPT axis was compared with that of levothyroxine. TPY3m increased TH levels when administered to both healthy and diabetic rats, normalizing thyroxine and triiodothyronine levels in T2DM and, unlike levothyroxine, without negatively affecting TSH levels or the expression of hypothalamic and pituitary genes responsible for TSH production. TPY3m pretreatment preserved the stimulatory effects of TRH on TH levels and thyroid gene expression. This indicates the absence of competition between TPY3m and endogenous TSH for TSH receptor activation and is supported by our in vitro results on TPY3m- and TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Morphological analysis of thyroid glands in diabetic rats after three-day TPY3m administration shows an increase in its functional activity without destructive changes. To summarize, TPY3m, with the activity of a partial allosteric agonist of the TSH receptor, was created as a prototype of drugs to correct thyroid insufficiency in T2DM. Full article

In recent years, fungal infections have emerged as a significant health concern across veterinary species, especially in livestock such as cattle, where fungal diseases can result in considerable economic losses, as well as in humans. In particular, Aspergillus species, notably Aspergillus flavus and Aspergillus versicolor, are opportunistic pathogens that pose a threat to both animals and humans. This study focuses on the synthesis and antifungal evaluation of novel 9-fluorenylmethoxycarbonyl (Fmoc)-protected 1,2,4-triazolyl-α-amino acids and their dipeptides, designed to combat fungal pathogens. More in detail, we evaluated their antifungal activity against various species, including Aspergillus versicolor (ATCC 12134) and Aspergillus flavus (ATCC 10567). The results indicated that dipeptide 7a exhibited promising antifungal activity against Aspergillus versicolor with an IC₅₀ value of 169.94 µM, demonstrating greater potency than fluconazole, a standard treatment for fungal infections, which showed an IC₅₀ of 254.01 µM. Notably, dipeptide 7a showed slightly enhanced antifungal efficacy compared to fluconazole also in Aspergillus flavus (IC₅₀ 176.69 µM vs. 184.64 µM), suggesting that this dipeptide might be more potent even against this strain. Remarkably, 3a and 7a are also more potent than fluconazole against A. candidus 10711. On the other hand, the protected amino acid 3a demonstrated consistent inhibition across all tested Aspergillus strains, but with an IC₅₀ value of 267.86 µM for Aspergillus flavus, it was less potent than fluconazole (IC₅₀ 184.64 µM), still showing some potential as a good antifungal molecule. Overall, our findings indicate that the synthesized 1,2,4-triazolyl derivatives 3a and 7a hold significant promise as potential antifungal agents in treating Aspergillus-induced diseases in cattle, as well as for broader applications in human health. Our mechanistic studies based on molecular docking revealed that compounds 3a and 7a bind to the same region of the sterol 14-α demethylase as fluconazole. Given the rising concerns about antifungal resistance, these amino acid derivatives, with their unique bioactive structures, could serve as a novel class of therapeutic agents. Further research into their in vivo efficacy and safety profiles is warranted to fully realize their potential as antifungal drugs in clinical and agricultural settings. Full article

Epoxy resin (EP) is an indispensable packaging material for batteries. Excellent thermal and flame-retardant properties of EP can ensure the safety performance of batteries. To solve the low-efficiency flame retardant of EP, nickel phenyl phosphate (NiPP) was synthesized and its surface was modified by polymerization of dopamine (PDA). [3-(hydroxy-phenyl-methylidene) imimine] triazole (DTA) was synthesized using 9,10-dihydro-9-oxygen-10-phosphophene-10-oxide (DOPO), 3-amino-1,2,4-triazole and p-hydroxybenzaldehyde. The hybrid flame retardance NiPP@PDA@DTA was further synthesized by self-assembly between the negative charge on the surface of DTA and the positive charge on the surface of modified NiPP@PDA. Then, NiPP@PDA@DTA was added to EP to prepare EP/NiPP@PDA@DTA composites. The results showed that the incorporation of NiPP@PDA@DTA promoted the residual yield at high temperatures. Furthermore, EP composites showed excellent flame retardancy when NiPP@PDA@DTA was added. The EP/4 wt% NiPP@PDA@DTA composites can reach UL-94 V0 grade with a limit oxygen index (LOI) of 33.7%. While the heat release rate (HRR), total release rate (THR), CO₂ production (CO₂P) and total smoke release (TSR) of EP/4 wt% NiPP@PDA@DTA composites decreased by 16.9%, 30.8%, 16.9% and 27.7% compared with those of EP. These improvements are mainly due to the excellent catalytic carbonization performance of Ni metal and P compounds. The azazole and phosphaphenanthrene groups have the effects of dilution quenching in the gas phase and cross-linking network blocking, as well as enhanced blowing-out effects. Full article