Search Results (27)

The exponential growth of the aged population worldwide is followed by an increase in the prevalence of age-related disorders. Oxidative stress plays central role in damage accumulation during ageing and cell senescence. Thus, a major target of today’s anti-ageing research has been focused on antioxidants counteracting senescence. In the current work, six novel 5,7,8-trimethyl-1,4-benzoxazine/catechol or resorcinol hybrids were synthesized connected through a methoxymethyl-1,2,3-triazolyl or a 1,2,3-triazoly linker. The compounds were evaluated for their antioxidant capacity in a cell-free system and for their ability to reduce intracellular ROS levels in human skin fibroblasts, both young (early-passage) and senescent. The most efficient compounds were further tested in these cells for their ability to induce the expression of the gene heme oxygenase-1 (ho-1), known to regulate redox homeostasis, and cellular glutathione (GSH) levels. Overall, the two catechol derivatives were found to be more potent than the resorcinol analogues. Furthermore, these two derivatives were shown to act coordinately as radical scavengers, ROS inhibitors, ho-1 gene expression inducers, and GSH enhancers. Interestingly, one of the two catechol derivatives was also found to enhance human skin fibroblast viability. The properties of the synthesized compounds support their potential use in cosmetic applications, especially in products targeting skin ageing. Full article

A synthetic pathway to a novel 4-aryl-3,4-dihydro-2H-1,4-benzoxazine scaffold was developed and a series of compounds based on the scaffold were synthesised as potential anticancer agents. The 4-aryl-substituted compounds were prepared via Buchwald–Hartwig cross-coupling between substituted bromobenzenes and various 1,4-benzoxazines, which in turn were generated from a cascade hydrogenation and reductive amination one-pot reaction. These analogues exhibited moderate to good potency against various cancer cell lines. Structure–activity relationship analysis indicated that the inclusion of hydroxyl groups on ring A and ring B was beneficial to biological activity, while having a para-amino group on ring C significantly enhanced potency. Molecule 14f displayed the most potent anticancer activity (IC₅₀ = 7.84–16.2 µM against PC-3, NHDF, MDA-MB-231, MIA PaCa-2, and U-87 MG cancer cell lines), indicating its potential as a lead compound for further structural optimisation. All the synthesised compounds were fully characterised with NMR, HMRS, and IR. The novel benzoxazine scaffold described in this study holds promise and deserves further in-depth studies. Full article

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment. Full article

A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its (S)-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by ¹H, ¹⁹F, and ¹³C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC. Antiviral evaluation of the synthesized compounds has shown that the replacement of purine with a pyrimidine fragment leads to a decrease in the anti-herpesvirus activity compared to the lead compound, purine conjugate. The studied compounds did not exhibit significant activity against influenza A (H1N1) virus. Full article

This work explores the strategy of incorporating a highly substituted reactive flame retardant into a benzoxazine moiety. For this purpose, a DOPO-based flame retardant received a chain extension via reaction with ethylene carbonate. It was then reacted with phloretic acid to obtain a diphenol end-capped molecule, and further reacted with furfurylamine and paraformaldehyde to obtain a benzoxazine monomer via a Mannich-like ring closure reaction. This four-step synthesis yielded a partly bio-based halogen-free flame retardant benzoxazine monomer (DOPO-PA-fa). The successful synthesis was proven via NMR, IR and MS analysis. The polymerization behavior was monitored by DSC and rheological analysis both showing the polymerization starts at 200 °C to yield pDOPO-PA-fa. pDOPO-PA-fa has a significant thermal stability with a residual mass of 30% at 800 °C under ambient atmosphere. Furthermore, it reached a V-0 rating against small flames and an OI of 35%. Blended with other benzoxazines, it significantly improves their thermal stability and fire resistance. It emphasizes its potential as flame retardant agent. Full article

This work is devoted to the influence of phosphazene modifiers with different substituents on the curing process, thermal properties and flammability of benzoxazine resin. Novel catalysts with m-toluidine substituents were introduced. The catalytic activity of studied phosphazene compounds decreased in the row: hexachlorocyclotriphosphazene (HCP) > tetra m-toluidine substituted phosphazene PN-mt (4) > hexa m-toluidine substituted phosphazene PN-mt (6) > hexaphenoxycyclotriphosphazene (HPP), where HPP is totally inactive. Two types of catalysis: basic and acid were proposed. A brief study of resulting properties of polybenzoxazines was presented. The addition of any studied modifier caused the decrease of glass transition temperature and thermal stability of polymers. The morphology of cured compositions was characterized by matrix-dispersion phase structure. All phosphazene containing polybenzoxazines demonstrated the improved flame resistance. Full article

A novel type of phosphazene containing an additive that acts both as a catalyst and as a flame retardant for benzoxazine binders is presented in this study. The synthesis of a derivative of hexachlorocyclotriphosphazene (HCP) and meta-toluidine was carried out in the medium of the latter, which made it possible to achieve the complete substitution of chlorine atoms in the initial HCP. Thermal and flammability characteristics of modified compositions were investigated. The modifier catalyzes the process of curing and shifts the beginning of reaction from 222.0 °C for pure benzoxazine to 205.9 °C for composition with 10 phr of modifier. The additive decreases the glass transition temperature of compositions. Achievement of the highest category of flame resistance (V-0 in accordance with UL-94) is ensured both by increasing the content of phenyl residues in the composition and by the synergistic effect of phosphorus and nitrogen. A brief study of the curing kinetics disclosed the complex nature of the reaction. An accurate two-step model is obtained using the extended Prout–Tompkins equation for both steps. Full article

Oxidative stress is often the cause of a wide range of human chronic pathologies including, but not limited to, stroke and cardiovascular and neurodegenerative diseases. In this setting, increasing efforts are currently being devoted to the design and synthesis of new derivatives with enhanced antioxidant efficacy. Among all the potential molecules of interest, synthetic nitrone spin-traps have attracted a great deal of research attention, particularly due to their dual function as effective inhibitors of oxidative stress and damage and as analytical tools for the detection and characterization of free radicals by means of the electron paramagnetic resonance (EPR) spectroscopy spin trapping technique. In this study, two derivatives of benzoxazinic nitrones (3-aryl-2H-benzo[1,4]oxazin-N-oxides) bearing an electron-withdrawing methyl-acetate group on the benzo moiety (in para and meta positions with respect to the nitronyl function) were synthesized. Their in vitro antioxidant activity was evaluated by means of the α,α-diphenyl-β-picrylhydrazyl radical (DPPH) scavenging assay, and their inhibitory effects on the erythrocyte hemolysis induced by the water-soluble free radical initiator 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) compared. In addition, EPR was employed to monitor the decay profiles of DPPH to evaluate the kinetic behavior of the different antioxidants tested. Results showed that the presence and the position of the electron-withdrawing methyl-acetate group strongly affects the radical scavenging activity of nitrones. In particular, the newly synthesized para-substituted derivative, when compared to both the meta-substituted isomer and the unsubstituted parent compound, acts as a more effective antioxidant both in cell and cell-free systems. Overall, these results clearly show that the introduction of an electron-withdrawing group on the phenyl moiety significantly increased the antioxidant capacity of benzoxazinic nitrones, thus showing exciting opportunities in the search for new therapeutic agents in the treatment of diseases associated with oxidative stress. Full article

In this study, 2-(aminomethyl)phenol and its derivatives, the reactants for 2-substituted 1,3-benzoxazines, are synthesized by HCl hydrolysis from the typical benzoxazines. The phenol/aniline-based mono-oxazine benzoxazine, PH-a, and the bisphenol A/aniline-based bis-oxazine benzoxazine, BA-a, are used as examples to demonstrate the feasibility of this new approach. Their chemical structures are characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) and Raman spectroscopies, and are further verified by elementary analysis. Their thermal properties are studied by differential scanning calorimetry (DSC). These two 2-(aminomethyl) phenolic derivatives are reacted with paraformaldehyde to close the oxazine rings. A benzoxazine with a phenyl substituent at the 2-position of the oxazine ring is obtained from the 2-((phenylamino)methyl)phenol (hPH-a) and benzaldehyde. All these results highlight the success of the HCl hydrolysis and the formation of stable intermediates, namely 2-(aminomethyl) phenolic derivatives, from readily available benzoxazine monomers. This further demonstrates the feasibility of using these intermediates as reactants for a novel benzoxazine synthesis. Full article

We developed an efficient method for synthesis of substituted N-benzoylindole via Pd(II)-catalyzed C–H functionalization of substituted N-(2-allylphenyl)benzamide. The reaction showed a broad substrate scope (including N-acetyl and N-Ts substrates) and substituted indoles were obtained in good to excellent yields. The most distinctive feature of this method lies in the high selectivity for N-benzoylindole over benzoxazine, and this is the first example of Pd(II)-catalyzed synthesis of substituted N-benzoylindole. Notably, this new method was applied for the synthesis of key intermediate of indomethacin. Full article

The KOH-promoted chemodivergent benzannulation of ortho-fluorobenzamides with 2-propyn-1-ol can afford either 1,4-benzoxazepin-5(4H)-ones or 1,3-benzoxazin-4(4H)-ones in good yields with high selectivity, depending greatly upon the use of solvents. In the case of using DMSO, the intermolecular benzannulation produced seven-membered benzo-fused heterocycles of 1,4-benzoxazepin-5(4H)-ones, whereas in MeCN, the six-membered benzo-fused heterocycles of 1,3-benzoxazin-4(4H)-ones were formed. The KOH-promoted benzannulation proceeded most probably through the C–F nucleophilic substitution of ortho-fluorobenzamides with 2-propyn-1-ol to give the intermediate of ortho-[(2-propynyl)oxy]benzamide, which underwent the intramolecular hydroamidation in a different manner to afford either seven- or six-membered benzo-fused heterocycles. Full article

A one-pot route to 2-alkyl and 2-aryl-4H-benzo[d][1,3]oxazin-4-ones (also known as 4H-3,1-benzoxazin-4-ones) has been developed and studied. The method involves the reaction of aryl-substituted anthranilic acids with orthoesters in ethanol catalyzed by acetic acid. Additionally, we have also investigated the reaction under microwave conditions. Not all of the substrates were successful in yielding the target heterocycles as some of the reactions failed to undergo the final elimination. This process led to the isolation of (±)-2-alkyl/aryl-2-ethoxy-1,2-dihydro-4H-benzo[d][1,3]oxazin-4-ones. The formation of the dihydro analogs correlated with the electron density on the aromatic ring: Electron-donating groups favored the 4H- benzo[d][1,3]oxazin-4-ones, while electron-withdrawing groups tended to favor the dihydro product. Substituting a pyridine ring for the benzene ring in the substrate acid suppressed the reaction. Full article

The dominance of safener can unite with herbicides acquiring the efficient protection of crop and qualifying control of weeds in agricultural fields. In order to solve the crop toxicity problem and exploit the novel potential safener for fenoxaprop-P-ethyl herbicide, a series of trichloromethyl dichlorobenzene triazole derivatives were designed and synthesized by the principle of active subunit combination. A total of 21 novel substituted trichloromethyl dichlorobenzene triazole compounds were synthesized by substituted aminophenol and amino alcohol derivatives as the starting materials, using cyclization and acylation. All the compounds were unambiguously characterized by IR, ¹H-NMR, ¹³C-NMR, and HRMS. A greenhouse bioassay indicated that most of the title compounds could protect wheat from injury caused by fenoxaprop-P-ethyl at varying degrees, in which compound 5o exhibited excellent safener activity at a concentration of 10 μmol/L and was superior to the commercialized compound fenchlorazole. A structure–activity relationship for the novel compounds was determined, which demonstrated that those compounds containing benzoxazine groups showed better activity than that of oxazole-substituted compounds. Introducing a benzoxazine fragment and electron-donating group to specific positions could improve or maintain the safener activity for wheat against attack by the herbicide fenoxaprop-P-ethyl. A molecular docking model suggested that a potential mechanism between 5o and fenoxaprop-P-ethyl is associated with the detoxication of the herbicide. Results from the present work revealed that compound 5o exhibited good crop safener activities toward wheat and could be a promising candidate structure for further research on wheat protection. Full article

A straightforward and novel method for transformation of readily available 1,3-benzoxazines to secondary phosphonates and α-aminophosphonates using boron trifluoride etherate as catalyst is developed. The formation of phosphonates proceeds through ortho-quinone methide (o-QM) generated in situ, followed by a phospha-Michael addition reaction. On the other hand, the α-aminophosphonates were obtained by iminium ion formation and the subsequence nucleophilic substitution of alkylphosphites. This method can be also used for the preparation of o-hydroxybenzyl ethers through oxa-Michael addition. Full article

Poly(2,6-dimethyl phenyl oxide) (PPO) is known for its low dissipation factor. To achieve insulating materials with low dissipation factors for high-frequency communication applications, a telechelic oligomer-type benzoxazine (P-APPO) and a main-chain type benzoxazine polymer (BPA-APPO) were prepared from an amine end-capped oligo (2,6-dimethyl phenylene oxide) (APPO). The APPO was prepared from a nucleophilic substitution of a phenol-end capped oligo (2,6-dimethyl phenylene oxide) (a commercial product, SA 90) with fluoronitrobenzene, and followed by catalytic hydrogenation. After self-curing or curing with a dicyclopentadiene-phenol epoxy (HP 7200), thermosets with high-T_g and low-dissipation factor can be achieved. Furthermore, the resulting epoxy thermosets show better thermal and dielectric properties than those of epoxy thermoset cured from its precursor SA90, demonstrating it is a successful modification in simultaneously enhancing the thermal and dielectric properties. Full article