Search Results (117)

Benzoxazine resins are gaining attention for their impressive thermal stability, low water uptake, and strong mechanical properties. In this work, two new bio-based benzoxazine monomers were developed using renewable arbutin: one combined with 3-(2-aminoethylamino) propyltrimethoxysilane (AB), and the other with furfurylamine (AF). Both were synthesized using a simple Mannich-type reaction and verified through FT-IR and ¹H-NMR spectroscopy. By blending these monomers in different ratios, copolymers with adjustable thermal, dielectric, and surface characteristics were produced. Thermal analysis showed that the materials had broad processing windows and cured effectively, while thermogravimetric testing confirmed excellent heat resistance—especially in AF-rich blends, which left behind more char. The structural changes obtained during curing process were monitored using FT-IR, and XPS verified the presence of key elements like carbon, oxygen, nitrogen, and silicon. SEM imaging revealed that AB-based materials had smoother surfaces, while AF-based ones were rougher; the copolymers fell in between. Dielectric testing showed that increasing AF content raised both permittivity and loss, and contact angle measurements confirmed that surfaces ranged from water-repellent (AB) to water-attracting (AF). Overall, these biopolymers (AB/AF copolymers) synthesized from arbutin combine environmental sustainability with customizability, making them strong candidates for use in electronics, protective coatings, and flame-resistant composite materials. Full article

The efficient employment of chiral porous organic cages (POCs) for asymmetric catalysis is of great significance. In this work, we have synthesized a chiral N-rich organic cage constructed through chiral (S, S)-1,2-cyclohexanediamine and benzene-1,3,5-tricarbaldehyde utilizing dynamic imine chemistry according to the literature. Following reduction with NaBH₄, the resulting amine-based POCs (RCC3) feature appended chiral diamine moieties capable of coordinating Cu²⁺ cations. This Cu²⁺ coordination provides RCC3 with excellent enantioselectivity as a supramolecular nanoreactor in asymmetric decarboxylative Mannich reactions, providing up to 94% ee of the product. We found that the spatial distribution of chiral amine sites and the coordination of Cu²⁺ in the RCC3 have a significant impact on catalytic activity, especially enantioselectivity. This work provides insights into the structure–function relationship within supramolecular catalytic systems Full article

A series of novel N-Mannich bases derived from a dimethylpyridine–1,2,4-triazole hybrid was synthesized and evaluated in vitro for cytotoxic activity on several human gastrointestinal cancer cells (EPG, Caco-2, LoVo, LoVo/Dx, and HT-29). Compound 6 bearing a phenyl group at the N-4 position and a 4-methylphenyl piperazine moiety at the N-2 position of the 1,2,4-triazole-3-thione scaffold exerted good cytotoxic activities on EPG and Caco-2 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal colonic epithelial cells (CCD 841 CoTr). Further evaluation revealed the good ability of compound 6 to inhibit the efflux function of P-glycoprotein in P-gp-expressing cell lines (HT-29, LoVo, and LoVo/Dx). Moreover, compound 6 induced apoptotic cell death through a significant increase in the caspase-3 and p53 protein levels in HT-29 cells. Finally, the molecular docking method was applied to explain our experimental findings. The molecular modeling study based on Density Functional Theory (DFT) and the Quantum Theory of Atoms in Molecules (QTAIM) analysis provided insight into the geometric and electronic structure properties of the compounds. Full article

Kynurenic acid (KYNA) derivatives condensed with an aromatic ring (tricyclic KYNA derivatives) have been successfully synthesized, and the reactivity of these analogues has been investigated in the modified Mannich reaction resulting in new Mannich bases. The N,N-dimethyl-ethylenediamine analogues of the tricyclic KYNA derivatives have also been successfully synthesized, and their reactivity in the modified Mannich reaction was investigated. The synthesized ring systems bear resemblance to molecules previously investigated as G-quadruplex binding agents. Based on this similarity, the synthesized tricyclic KYNA derivatives could be investigated as potential antiviral and anticancer molecules. 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

Calix[4]resorcinarenes are polyhydroxylated macrocyclic compounds with four units of resorcinol. These compounds can be derivatized through modifications at the upper rim, allowing reactivity with secondary amines to produce Mannich base derivatives via Mannich-type aminomethylation reactions. In this paper, we report the reaction of C-tetra(propyl)calix[4]resorcinarene with piperidine in acetonitrile. The aminomethylated compound C-2,8,14,20-tetra(propyl)-5,11,17,23-tetrakis(N–(piperidine)methyl)calix[4]resorcinarene was obtained with a 52% yield, with an exact mass of 1044.6994 u and a mass error of 7.6 ppm. The reaction progress and product formation were monitored by RP-HPLC, and the compound was characterized using LC ESI-TOF/MS, one- and two-dimensional ¹H and ¹³C NMR, and FTIR spectroscopy. Chromatographic and spectroscopy data are presented and discussed. Full article

There is a strong demand for new and efficient antiviral compounds. A series of 2-hydroxy-1,4-naphthoquinone Mannich bases were screened for their HIV-1-RNase H inhibitory activity. An HIV-1-RNase H assay was used to study the RNase H inhibition by the test compounds. Docking of active derivatives into the active site of the enzyme was carried out. Compounds 1e and 2k showed distinctly higher HIV-1-RNase H inhibitory activity (IC₅₀ = 2.8–3.1 µM) than the known inhibitors RDS1759 and compound 13. The binding mode and possible interactions of 1e and 2k with the HIV-1-RNase H active site were determined using molecular docking, which led to the identification of salient and concealed pharmacophoric features of these molecules. The docking analysis revealed that there are significant differences in the binding mode of these compounds within the active site of the target enzyme. A selection of HIV-1-RNase H-inhibitory Mannich bases was tested for antiviral activity against HIV-1, and compound 2k showed the highest activity at low toxicity to host cells. The lawsone Mannich bases 1e and 2k also underwent a preliminary screening for activity against SARS-CoV-2, and compound 1e was found to inhibit SARS-CoV-2 replication (IC₅₀ = 11.2 µM). Full article

The immobilisation of essential oil components (EOCs) on food-grade supports is a promising strategy for preserving liquid foods without the drawbacks of direct EOC addition such as poor solubility, high volatility, and sensory alterations. This study presents a novel method for covalently immobilising EOCs, specifically thymol and carvacrol, on SiO₂ particles (5–15 µm) using the Mannich reaction. This approach simplifies conventional covalent immobilisation techniques by reducing the steps and reagents while maintaining antimicrobial efficacy and preventing compound migration. The antimicrobial effectiveness of the EOC–SiO₂ system, applied as an additive, was tested against foodborne pathogens (Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes) inoculated into phosphate buffer solution and fresh apple juice. The results showed high antimicrobial activity, with inactivation exceeding 4-log reductions, depending on the EOC type, target microorganism, and medium. Moreover, the addition of functionalised particles did not affect the juice organoleptic properties. This study demonstrates that the Mannich reaction is an effective method for developing antimicrobial systems based on the covalent immobilisation of EOCs on silica particles, and offers a practical solution for food preservation without compromising food quality. Full article

Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as a promising target for disrupting the metabolic adaptability of tumor cells. This study explores the potential of the Mannich base derived from lawsone (MB-6a) to interfere with PKM2 enzymatic activity both in vitro and in silico. Methods: The antiproliferative potential of MB-6a was tested using MTT assay in various cell lines, including SCC-9, Hep-G2, HT-29, B16-F10, and normal human gingival fibroblast (HGF). The inhibition of PKM2 mediated by MB-6a was assessed using an LDH-coupled assay and by measuring ATP production. Docking studies and molecular dynamics calculations were performed using Autodock 4 and GROMACS, respectively, on the tetrameric PKM2 crystallographic structure. Results: The Mannich base 6a demonstrated selective cytotoxicity against all cancer cell lines tested without affecting cell migration, with the highest selectivity index (SI) of 4.63 in SCC-9, followed by B16-F10 (SI = 3.9), Hep-G2 (SI = 3.4), and HT-29 (SI = 2.03). The compound effectively inhibited PKM2 glycolytic activity, leading to a reduction of ATP production both in the enzymatic reaction and in cells treated with this naphthoquinone derivative. MB-6a showed favorable binding to PKM2 in the ATP-bound monomers through docking studies (PDB ID: 4FXF; binding affinity scores ranging from −6.94 to −9.79 kcal/mol) and MD simulations, revealing binding affinities stabilized by key interactions including hydrogen bonds, halogen bonds, and hydrophobic contacts. Conclusions: The findings suggest that MB-6a exerts its antiproliferative activity by disrupting cell glucose metabolism, consequently reducing ATP production and triggering energetic collapse in cancer cells. This study highlights the potential of MB-6a as a lead compound targeting PKM2 and warrants further investigation into its mechanism of action and potential clinical applications. Full article

The purpose of this study was to design nanocarriers with small-size and antioxidant properties for the effective encapsulation of curcumin. Here, procyanidins, vanillin, and amino acids were used to successfully prepare nanocarriers of a controllable size in the range of 328~953 nm and to endow antioxidant ability based on a one-step self-assembly method. The reaction involved a Mannich reaction on the phenolic hydroxyl groups of procyanidins, aldehyde groups of vanillin, and amino groups of amino acids. Subsequently, curcumin nanoparticles were prepared by loading curcumin with this nanocarrier, and the encapsulation efficiency of curcumin was 85.97%. Compared with free curcumin, the antioxidant capacity and photothermal stability of the embedded curcumin were significantly improved, and it could be slowly released into simulated digestive fluid. Moreover, using the corticosterone-induced PC12 cell injury model, the cell viability increased by 23.77% after the intervention of curcumin nanoparticles, and the cellular antioxidant capacity was also significantly improved. The nanoparticles prepared in this work can effectively improve the solubility, stability, and bioactivity of curcumin, which provides a reference for the embedding and delivery of other hydrophobic bioactive compounds. Full article

The reaction between glycine-type aminonaphthol derivatives substituted with 2- or 1-naphthol and indole or 7-azaindole has been tested. Starting from 2-naphthol as a precursor, the reaction led to the formation of ring-closed products, while in the case of a 1-naphthol-type precursor, the desired biaryl ester was isolated. The synthesis of a bifunctional precursor starting from 5-chloro-8-hydroxyquinoline, morpholine, and ethyl glyoxylate via modified Mannich reaction is reported. The formed Mannich base 10 was subjected to give bioconjugates with indole and 7-azaindole. The effect of the aldehyde component and the amine part of the Mannich base on the synthetic pathway was also investigated. In favor of having a preliminary overview of the structure-activity relationships, the derivatives have been tested on cancer and normal cell lines. In the case of bioconjugate 16, as the most powerful scaffold in the series bearing indole and a 5-chloro-8-hydroxyquinoline skeleton, a potent toxic activity against the resistant Colo320 colon adenocarcinoma cell line was observed. Furthermore, this derivative was selective towards cancer cell lines showing no toxicity on non-tumor fibroblast cells. Full article

The synthesis and characterization of two novel diastereomeric Mannich bases was carried out from the reaction of the cyclic aminal (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo[8.8.1.1.^8,170.^2,70.^11,16]icosane 1 and p-cresol 2a and 4-methoxyphenol 2b in a water/dioxane mixture. The title compounds (4a–b) are interesting because bearing two 3-(2-hydroxy-5-substitutedbenzyl)octahydro-1H-benzimidazol-1-yl]methyl} substituents joined to an arenol ring. The formation of these new Mannich bases in the reaction mixture can be explained by aminomethylation of previously reported di-Mannich base 2,2′-((hexahydro-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(methylene))bis(4-substituentphenol) 3a–b. NMR analysis demonstrated that compounds 4a–b were formed as diastereomeric mixtures. Subsequent experiments revealed that at longer reaction times, the percentage yield of these new products increased considerably (yield percentages up to 22–27%), suggesting a nucleophilic competition between the p-substituted phenols and Mannich bases of type 3 for aminal 1. Full article

Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2–5 were determined by X-ray analysis. Full article

Alkoxyalkylation and hydroxyalkylation methods utilizing oxo-compound derivatives such as aldehydes, acetals or acetylenes and various alcohols or water are widely used tools in preparative organic chemistry to synthesize bioactive compounds, biosensors, supramolecular compounds and petrochemicals. The syntheses of such molecules of broad relevance are facilitated by acid, base or heterogenous catalysis. However, degradation of the N-analogous Mannich bases are reported to yield alkoxyalkyl derivatives via the retro-Mannich reaction. The mutual derivative of all mentioned species are quinone methides, which are reported to form under both alkoxy- and aminoalkylative conditions and via the degradation of the Mannich-products. The aim of this review is to summarize the alkoxyalkylation (most commonly alkoxymethylation) of electron-rich arenes sorted by the methods of alkoxyalkylation (direct or via retro-Mannich reaction) and the substrate arenes, such as phenolic and derived carbocycles, heterocycles and the widely examined indole derivatives. Full article

Bacterial infections are the second-leading cause of death, globally. The prevalence of antibacterial resistance has kept the demand strong for the development of new and potent drug candidates. It has been demonstrated that Src protein tyrosine kinases (TKs) play an important role in the regulation of inflammatory responses to tissue injury, which can trigger the onset of several severe diseases. We carried out a search for novel Src protein TK inhibitors, commencing from reported highly potent anti-bacterial compounds obtained using the Mannich reaction, using a combination of e-pharmacophore modeling, virtual screening, ensemble docking, and core hopping. The top-scoring compounds from ligand-based virtual screening were modified using protein structure-based design approaches, and their binding to the Src homology-2 domain of p56^lck TK was predicted using ensemble molecular docking. We have prepared a database of 202 small molecules and have identified six novel top hits that can be subjected to further investigation. We have also performed in silico ADMET property prediction for the hit compounds. This combined computer-aided drug design approach can serve as a starting point for identifying novel TK inhibitors that could be further subjected to in vitro studies and validation of antimicrobial activity. Full article