Search Results (144)

Phenolic acids are widely known for their antioxidant and biological properties, which make them attractive scaffolds for structural modification. In this short note, we report the synthesis of a new 3,4-di-glucosylated caffeic acid analogue. The (E)-3-(3,4-di-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyloxy)phenyl) acrylic acid was obtained through a two-step synthesis, starting with a phase-transfer-catalyzed glycosylation of 3,4-dihydroxybenzaldehyde with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide followed by a Dobner-modified Knoevenagel condensation. Consistent with the 2-O-acetyl neighbouring participation and the resulting Walden-type inversion at the anomeric centre, both glucopyranosyl units were assigned the β-configuration. Full article

The use of styrylium dyes as organic nonlinear optical materials in many photonics domains has been the subject of research for decades. It has been noted that over time, research has also looked into the biological activity of styrylium dyes, namely their antibacterial effects, as well as attempts to establish links between structure and property by choosing particular structural pieces. These investigations’ scope is still very limited. Therefore, our main goal was to synthesize a styrylium compound with antimicrobial potential. A novel styrylquinolinium compound (D) was synthesized using Knoevenagel condensation. Spectroscopic techniques, including IR, 1D and 2D NMR (COSY, HSQC, and HMBC), HRMS spectra, and X-ray analysis, were used to confirm its structure. The antimicrobial and anti-inflammatory activity of the compound was assessed. The compound was found to have very good antimicrobial activity against five Gram-positive strains, three Gram-negative strains, and fungi. The most pronounced effect of the compound was against Escherichia coli and Pseudomonas aeruginosa. The compound’s anti-inflammatory activity was evaluated through its ex vivo immunohistochemistry. DFT calculations, such as geometry optimization, Molecular Electrostatic Potential (MEP), HOMO–LUMO, reactivity parameters and molecular docking simulation were applied to investigate the electronic features of the compound and confirm the biological activity. The compound (D) demonstrated a promising antibacterial and immunomodulatory profile. Its ability to induce IL-1β and at the same time moderately reduce NOS3 can be considered as a controlled adaptation of the immune response, especially in cases requiring local immune activation. Docking simulation revealed that (D) binds effectively to the active site of the bacterial protein, supporting the experimental findings of the compound’s antibacterial activity. Full article

A novel series of benzoxazole-derived iminocoumarins was synthesized via a Knoevenagel condensation and fully characterized using NMR, UV–Vis spectroscopy, and computational methods. Their photophysical properties were systematically examined in solvents of varying polarity, revealing pronounced effects of both substituents and solvent environment on absorption maxima and intensity. Derivatives bearing electron-donating substituents on the coumarin core exhibited distinct and reversible pH-responsive spectral shifts, confirming their potential as optical pH probes. Experimental pK_a values derived from absorption titrations showed excellent agreement with DFT-calculated data, validating the proposed protonation-deprotonation equilibria and associated electronic structure changes. Structure–property relationships revealed that electron-donating groups enhance intramolecular charge transfer, while electron-withdrawing substituents modulate spectral response and stability. In parallel, the compounds were evaluated for antiproliferative, antiviral, and antifungal activities in vitro. Strong electron-donating substituents were associated with potent but non-selective cytotoxicity, whereas derivatives bearing electron-withdrawing groups displayed moderate and more selective antiproliferative effects against leukemia cell lines. Antifungal screening revealed moderate inhibition of phytopathogenic fungi, particularly for compounds with electron-withdrawing or methoxy substituents. Overall, these findings demonstrate that benzoxazole iminocoumarins represent a promising class of multifunctional heterocycles with potential applications as optical pH sensors and scaffolds for bioactive compound development. Full article

The present study focuses on the kinetics of the Knoevenagel condensation reaction between 7-methoxy-1-tetralone (1) and glyoxylic acid (2), catalyzed by potassium tert-butoxide in tert-butanol as a solvent, using a batch-type system under nitrogen atmosphere. The objective of this study was to synthesize the product (E)-2-(7-methoxy-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene) acetic acid (3). The reaction was conducted under controlled temperature conditions (65 °C, 75 °C and 85 °C), considering five specified time intervals to monitor its progress by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The kinetic data obtained was analyzed through three different mathematical methods: integral, differential, and nonlinear regression method, in order to determine the most suitable kinetic model. Applying the power law, the findings indicated that the pseudo-second order model, which was estimated via nonlinear regression, showed the best fit with the experimental data, characterized by minimal discrepancy between the calculated and observed values. The kinetic constants (k) obtained at temperatures of 65 °C, 75 °C and 85 °C were 0.89, 1.77 and 3.42 mL mmol⁻¹ min⁻¹, respectively. The pre-exponential factor (A) was calculated to be 2.194 × 10¹⁰ mL mmol⁻¹ min⁻¹, and the activation energy (Ea) was determined to be 67.22 kJ mol⁻¹. The product yield at these temperatures was 17.01%, 81.40% and 72.59%, respectively. The final product was characterized by GC-MS, FTIR, and UV-Vis. In conclusion, the kinetic study of the reaction was able to determine the optimal Knoevenagel condensation reaction conditions between (3) and (2) catalyzed by potassium tert-butoxide, and to facilitate understanding of the mechanism involved. Full article

This work reports progress in the semi-synthetic modification of cassane-type diterpenes isolated from Coulteria platyloba, a plant of ethnopharmacological relevance. The approach involves a sequence of transformations, including oxidative aromatization, ring opening, and Knoevenagel condensation, to generate key intermediates for further diversification. Preliminary studies demonstrated the feasibility of organocatalytic reactions under trienamine activation, including a successful Diels–Alder cycloaddition. The initial steps were achieved with good yields and high purity, underscoring the potential of this strategy to access novel molecular scaffolds through efficient and sustainable methods aligned with the principles of Diversity-Oriented Synthesis (DOS). Full article

Dicyanovinyl (DCV) oligothiophenes are interesting materials due to their unique optical and electronic properties. They are relatively easy to prepare using Knoevenagel condensation reactions from the corresponding aldehydes. Understanding their optical and electrochemical characteristics is important for both building structure/property relationships and for optimizing their performance in various applications. We report on the electrochemical and photophysical properties of three oligothiophenes end-capped with dicyanovinyl -CH=C(CN)₂ or DCV groups. The compounds included in this study are DCV-T-DCV (1), DCV-2T-DCV (2), and DCV-3T-DCV (3), where T represents one thiophene unit. Introduction of the DCV groups into oligothiophenes results in unique evolution of their electrochemical and optical behavior. First, new reversible two-electron reduction processes in the series DCV-nT-DCV start to appear with a gradual increase in the reduction potential with an increasing number of thiophene units. This was consistent with the electronic spectroscopic results. These results demonstrate that the DCV groups can be used in molecular design and fine-tuning of the optical and redox properties of oligothiophene and presumably this strategy can be extended to other conjugated organic molecules. We also report on the photophysical and vibrational spectroscopic properties of these compounds. The C=C stretching bands in Raman and IR spectra reveal more quinoidal nature in shorter molecules and more dominant benzoidal character in longer molecules. The DCV-induced modulation of electrochemical, optical, and vibrational properties highlights their potential in diverse optoelectronic applications. Full article

N-vinylindoles have attracted attention for their promising role in medicinal chemistry. Therefore, developing new synthetic methods that enable access to diverse functionalized N-vinylindoles with potential pharmacological properties is highly valuable. 1-[2-aryl-1-(4,5-dihydro-1H-imidazol-2-yl)vinyl]-1H-indoles 2a-i were prepared via Knoevenagel condensation promoted by 1H-benzotriazole, and characterized by IR, NMR, and MS spectroscopic data as well as a single-crystal X-ray diffraction-based study of the representative derivative 2g. The obtained compounds 2a-i were screened for their cytotoxic potency against human cancer cell lines (HeLa, SKOV-3, AGS) and non-cancerous cell line (HaCaT) using the MTT assay. Additional apoptosis analysis and cell cycle assay on SKOV-3 cells were conducted. Their antimicrobial activity was determined using reference strains of S. aureus, E. coli, C. albicans, and C. glabrata. The potent inhibitory activity against AGE2-BSA/sRAGE interaction of selected N-vinylindoles 2b, 2d-f, and 2h-i was evaluated by ELISA assay. A facile approach has been developed for the synthesis of a novel class of N-vinylindoles. The preliminary structure–activity considerations indicated that the presence of substituents R, such as 4-bromophenyl (compound 2f) or 2-naphthyl (compound 2i) is optimal for anticancer activity and the AGE2-BSA/sRAGE interaction inhibition. The most prominent (Z)-1-[1-(4,5-dihydro-1H-imidazol-2-yl)-2-(naphthalen-2-yl)vinyl]-1H-indole (2i) was found to strongly arrest cell cycle in the SKOV-3 cell line in the subG0 phase, inducing apoptosis. Notably, derivative 2i also exhibited the highest activity against S. aureus and C. albicans strains within the tested series. These findings highlight the substantial potential of N-vinylindole derivative 2i as a lead compound for the development of anticancer drugs with additional inhibitory activity on the AGE/RAGE interaction. Full article

Using an environmentally friendly approach, we successfully synthesized an asymmetric monomethine cyanine dye, 7-chloro-1-ethyl-4-((3-ethylbenzo[d]thiazol-2(3H)-ylidene)methyl) quinolin-1-ium iodide, named CHLoris (CHL), via a modified Knoevenagel-type condensation. The reaction was carried out mechanochemically in an ethanol–water medium using 1-ethyl-2-methylbenzothiazolium iodide and 4,7-dichloro-1-ethylquinolin-1-ium iodide in the presence of sodium carbonate as a base and catalytic amounts of Hünig’s base. The UV/VIS absorption spectra of CHL in both the buffer solution and ethanol revealed the formation of aggregates in aqueous media. Density Functional Theory (DFT) and Time-Dependent DFT (TDDFT) calculations were employed to support the experimental findings further and provide insights into the self-association behavior of CHL in an aqueous solution. The photophysical properties of the dye were examined in the presence of DNA and RNA, and its performance was compared to that of the commercial dye Thiazole Orange (TO) under identical conditions. The results show that CHL is more sensitive towards RNA. Full article

This study introduces an efficient and sustainable catalytic system utilizing cobalt ferrite nanoparticles (CoFe₂O₄-NPs) for the synthesis of valuable 6-amino-2-oxo-4-phenyl (or 4-chlorophenyl)-1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives. Recognizing the limitations of traditional methods for the Biginelli reaction, we thoroughly characterized CoFe₂O₄-NPs, alongside individual iron oxide nanoparticles (Fe₂O₃-NPs) and cobalt oxide nanoparticles (CoO-NPs), using FTIR, XRD, TEM, SEM, XPS, TGA, and BET analysis. These characterizations revealed the unique structural, morphological, and physicochemical properties of CoFe₂O₄-NPs, including an optimized porous structure and significant bimetallic synergy between Fe and Co ions. Catalytic studies demonstrated that CoFe₂O₄-NPs significantly outperformed individual Fe₂O₃-NPs and CoO-NPs under mild conditions. While the latter only catalyzed the Knoevenagel condensation, CoFe₂O₄-NPs uniquely facilitated the complete Biginelli reaction. This superior performance is attributed to the synergistic electronic environment within CoFe₂O₄-NPs, which enhances reactant activation, intermediate stabilization, and proton transfer during the multi-step reaction. This work highlights the potential of CoFe₂O₄-NPs as highly efficient and selective nanocatalysts for synthesizing biologically relevant 1,2,3,4-tetrahydropyrimidines, offering a greener synthetic route in organic chemistry. Full article

A new π-conjugated acceptor–donor–acceptor small molecule, designed for applications in organic solar cells, containing a terthiophene core and indandione- and benzonitrile-based electron-withdrawing units, was synthesized via a multi-step process involving Suzuki–Miyaura cross-coupling and Knoevenagel condensation reactions. The structure was confirmed by NMR spectroscopy, HRMS, and its optoelectronic properties were evaluated by UV–vis spectroscopy and cyclic voltammetry. Full article

In this paper, we will present the synthesis of coumarins bearing a phosphonate group in the C-3 position of the coumarin skeleton and phosphacoumarin derivatives. The compounds were synthesized by Knoevenagel condensation. Notably, the synthetic difficulties in preparing phosphacoumarins have limited previous studies. Our approach allows us to efficiently produce these derivatives, opening the way to investigate their biological properties. The resulting compounds were fully characterized using spectroscopic techniques and high-resolution mass spectrometry. We then evaluated the cytotoxicity of the compounds against human colon cancer HT-29 tumor and CCD 841 CoTr normal colon epithelial cells. We compared these results with coumarin activity to assess the effect of the introduction of the phosphonate group on their cytotoxicity. In addition, we performed cell cycle analysis by flow cytometry and examined the antioxidant activity of the compounds by the DPPH and FRAP methods. Furthermore, we conducted ADME analysis to gain more insight into the pharmacokinetic properties of the tested coumarins. Our study is in line with current trends in the search for new compounds with potential anticancer properties. Although there are numerous reports in the scientific literature on the anticancer activity of coumarin derivatives, the cytotoxicity of synthetic derivatives with a phosphonate group has not been investigated to date. Full article

In this study, a series of (Z)- and (E)-2-substituted-3-ferrocene-acrylonitrile derivatives were synthesized, characterized, and evaluated in vitro for their anticancer and anti-migration properties. The compounds were synthesized via the Knoevenagel condensation of the appropriate benzyl cyanide or benzoyl acetonitrile with ferrocenecarboxaldehyde 1, producing isolated yields of 99 to 23%. The structures of the compounds were analyzed using IR, ¹H NMR, ¹³C{¹H} NMR, GC-MS, and UV/Vis spectroscopic methods. Single-crystal X-ray diffraction analysis of representative compounds 21, 27, and 29 demonstrated that the geometry of the double bond was that of the (Z)-isomer. For representative compound 33, the geometry of the double bond was that of the (E)-isomer. Additionally, the electrochemistry of the compounds was investigated using cyclic voltammetry. The cytotoxic and anti-migratory effects of these compounds were evaluated in the MCF-7 and MDA-MB-231 breast cancer cell lines, providing insight into the structure–activity relationships. Preliminary investigations of their anticancer activity revealed that several compounds exhibit moderate antiproliferative effects on cancer cell lines, with GI₅₀ values ranging from 23 to 44 μM for the MCF-7 cell line and from 9 to 41 μM for the MDA-MB-231 cell line. Moreover, compound (Z)-25 inhibited 13% of the migration activity of the metastatic MDA-MB-231 cell line. Full article

In this study, novel fluorescent 5-aryl-2-styryl-3H-indole derivatives were efficiently synthesized from 4-bromophenylhydrazine hydrochloride using the microwave-accelerated one-pot technique, which includes Fischer synthesis, Suzuki cross-coupling, and Knoevenagel condensation. The structural assignments of the synthesized compounds were based on ¹H, ¹³C, ¹⁵N, and ¹⁹F NMR; IR spectroscopy; and HRMS spectral data. The optical properties of the newly obtained styryl-indole dyes were studied using UV-vis and fluorescence spectroscopy, which clearly demonstrated that the derivatives substituted with electron-donating or -withdrawing groups exhibited varying emission shifts and quantum yields ranging from negligible to high. Full article

Fluorene has been an extremely valued building block for many chemical compounds for a number of years. As a result, it is possible to design and obtain compounds with precisely defined physicochemical properties adapted to selected applications. An extremely interesting derivative of fluorene, which has been enjoying increasing interest in recent years, is dibenzofulvene (DBF) and its further structural modifications. So far, a number of dibenzofulvene derivatives have been described in the literature. Many of the presented DBFs are extremely structurally complex, which is why the influence of substituents on the physicochemical properties of the final compounds is not easy to determine unequivocally. Therefore, in this article, an attempt was made to explain the influence of N-donor substituents on selected physicochemical properties of dibenzofulvene derivatives (A-1–A-6). Moreover, these properties were compared to the results obtained for unsubstituted fluorene. The studies conducted showed that small modifications of the fluorene structure towards dibenzofulvene derivatives significantly change the absorption and emission properties of the final compounds. Importantly, the abovementioned structural modifications strongly affect the electrochemical properties, significantly reducing the energy gap and causing the oxidation potential to decrease to 0.18–0.42 V. Moreover, the process itself becomes fully reversible. The experimentally determined values coincide with those obtained theoretically via DFT calculations. Full article