Search Results (1,586)

Background: Third-generation aromatase inhibitors (CYP19A1) are the mainstay of treatment for estrogen-receptor-positive breast cancer. This is because estrogen is required for cancer growth in approximately 70% of patients with this condition. Although potent and effective, aromatase inhibitors induce resistance and secondary effects, requiring treatment to be discontinued. This clinical limitation highlights the need to search for new molecules. Previous studies have led to the identification of a set of indole sulfonamide molecules that exhibit interesting activity against aromatase. Methods: Phenyl and benzyl sulfonamide derivatives with alkylated heterocycles linked by short methylene bridges were designed and synthesized. The aromatase inhibition and cytotoxicity were tested through in vitro assays. Molecular docking and dynamic simulations evaluated the interactions with the aromatase enzyme, while a target fishing strategy linked to gene associations relevant to breast cancer helped to uncover other targets. Results: All of the non-steroidal inhibitors synthesized showed significant activity. Compounds 3 and 9 demonstrated IC₅₀ values in the low micromolar range and selective action against MCF7 breast cancer cells over healthy lines. Computational studies confirmed stable and favorable aromatase binding. Target fishing identified EGFR and PTK2B as additional potential targets for a multi-target therapeutic strategy. Conclusions: Compounds 3 and 9 outperform indole-based inhibitors in their potency and selectivity, revealing strong therapeutic potential. Their binding affinity and specificity support further development. EGFR and PTK2B may enable a broader, multi-target approach. Full article

Ajuga bracteosa is a herb with high medicinal value and a low range of distribution. It is used in several herbal and traditional medicines, including diabetes. In the present study, we designed the methodology for the micropropagation of A. bracteosa from internodal segments. The highest shoot multiplication was achieved on Murashige and Skoog (MS) medium supplemented with 6-benzyl-amino-purine (BAP) (5.0 µM) + indole-3-acetic acid (IAA) (1.5 µM) + adenine sulphate (ADS) (15.0 µM), which produced the maximum number of 20.45 ± 0.12 shoots/explants with 6.43 ± 0.006 cm shoot length. Rooting in the microshoots was attained on half-strength MS medium containing indole-3-butyric acid (IBA) (1.5 µM), with the highest root number of 16.44 ± 0.015 roots/shoot, and root length of 2.25 ± 0.011 cm. To assess genetic fidelity, SCoT marker analysis was performed on nine randomly selected in vitro regenerated plantlets and the mother plant, all of which exhibited monomorphic banding patterns, confirming genetic stability. Scanning electron microscopy (SEM) reveals normal stomatal structure in the regenerated plants post-acclimatization, indicating successful physiological recovery. Furthermore, Gas Chromatography–Mass Spectrometry (GC-MS) analysis confirms the presence of major phytocompounds in both the in vitro regenerated plants and the mother plant, supporting the conservation of phytochemical integrity. Given the restricted distribution and overharvesting pressure on this species, the established protocol provides an efficient strategy for rapid, large-scale, and genetically stable propagation to support conservation and pharmaceutical utilization. Full article

As a continuation of our research on the synthesis and study of biological properties of new derivatives of 3-aminopyridin-2(1H)-ones, we investigated the Leuckart–Wallach and Eschweiler–Clarke reactions with selected 3-aminopyridin-2(1H)-ones and 3-(arylmethyl)pyridin-2(1H)-ones. It was found that under the conditions of the Leuckart–Wallach reaction with aromatic aldehydes in formic acid, mainly formamides of the indicated 3-aminopyridones are formed. The Eschweiler–Clarke reaction of 3-aminopyridin-2(1H)-ones and 3-(arylmethyl)pyridin-2(1H)-ones with an aqueous solution of formaldehyde result in the formation of tertiary N–benzyl(methyl)amino)-pyridin-2(1H)-ones in almost quantitative yield. The 3-aminopyridin-2(1H)-ones derivatives synthesized by us were used for the biological screening of cytoprotective activity in the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test to determine the viability of fibroblast cells isolated from the NIH/Swiss mouse embryo (NIH/3T3, Gibco). It was found that many of the studied compounds under the conditions of our experiment exhibited significant cytoprotective effects, thereby enhancing cell survival. Full article

Herein, a bi-functional composite photocatalyst was synthesized by integrating carbon nanotubes (CNTs) and graphitic carbon nitride (GCN) via a facile electrostatic self-assembly strategy. The resulting CNTs/GCN composite served dual roles as both a solid emulsifier and a photocatalyst, enabling highly efficient photocatalytic benzyl alcohol oxidation within a Pickering emulsion system. The relationship between emulsion droplet size and solid emulsifier dosage was investigated and optimized. The enhanced photocatalytic function was supported by an improved photocurrent response and reduced charge-transfer resistance, attributed to superior charge separation efficiency. Consequently, the benzyl alcohol conversion efficiency achieved in the Pickering emulsion system (58.9%) was three-fold of that observed in a traditional oil–water non-emulsion system (19.0%). Key active species were identified as photoholes, and an interfacial reaction mechanism was proposed. This work provides a new approach for extending photocatalytic applications in aqueous environments to diverse organic conversion reactions through the construction of multifunctional photocatalysts. Full article

Candidiasis arises from the proliferation of Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have previously identified the N-[(4-sulfamoylphenyl)methyl][1,1′-biphenyl]-4-carboxamide to have fungistatic and fungicidal properties, likely due to the hydrophobic biphenyl–chemical features affecting the structural organization of Candida spp. cell membrane. Here, we designed and synthesized a novel series of twelve 5-arylfuran-2-carboxamide derivatives bearing a new hydrophobic tail as bioisosteric replacement of the diphenyl fragment. Its antifungal effectiveness against C. albicans, C. glabrata, and C. parapsilosis, including ATCC and clinically isolated strains, was assessed for all compounds. The most active compound was N-benzyl-5-(3,4-dichlorophenyl)furan-2-carboxamide (6), with fungistatic and fungicidal effects against C. glabrata and C. parapsilosis strains (MIC = 0.062–0.125 and 0.125–0.250 mg/mL, respectively). No synergistic effects were observed when combined with fluconazole. Interestingly, fluorescent microscopy analysis after staining with SYTO 9 and propidium iodide revealed that compound 6 affected the cell membrane integrity in C. albicans strain 16. Finally, carboxamide 6 exhibited a dose-dependent cytotoxicity on erythrocytes, based on assessing the LDH release. Full article

In this study, using 70% anhydrous ethanol as the extraction solvent, Moringa oleifera Lam. seed powder was extracted with the microwave-assisted extraction method, followed by purification using macroporous adsorbent resin NKA-9. The purified glucosinolate was subsequently hydrolyzed with myrosinase. The glucosinolate and its enzymatic product were identified as 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (4-RBMG) and benzyl isothiocyanate (BITC) by UV–Vis, FT-IR, NMR, and MS. The bioactivities, including anti-oxidation, anti-inflammation, and anti-tumor activities of 4-RBMG and BITC, were systematically evaluated and compared. The results show that at 5–20 mg/mL, the anti-oxidation effects of 4-RBMG on DPPH and ABTS free radicals are superior to those of BITC. However, at the same concentrations, BITC has stronger anti-inflammatory and anti-tumor activities compared to 4-RBMG. Notably, at a concentration of 6.25 μmol/L, BITC significantly inhibited NO production with an inhibitory rate of 96.67% without cytotoxicity. Additionally, at a concentration of 40 μmol/L, BITC exhibited excellent inhibitory effects on five tumor cell lines, with the cell inhibitory rates of leukemia HL-60, lung cancer A549, and hepatocellular carcinoma HepG2 exceeding 90%. This study provides some evidence that the enzymatic product, BITC, shows promise as a therapeutic agent for tumor suppression and inflammation reduction. Full article

Background/Objectives: Leishmaniasis is a zoonotic and anthropozoonotic disease with significant public health impact worldwide and is classified as a neglected tropical disease. The search for new affordable treatments, particularly oral and/or topical ones that are easy to administer and have fewer side effects, remains a priority for the scientific community in this field of research. In previous investigations, 3-alkoxy-1-benzyl-5-nitroindazole derivatives showed remarkable in vitro results against Leishmania species, and predictions of absorption, distribution, metabolism, excretion, and toxicity properties, as well as pharmacological scores, of the compounds classified as active were superior to those of amphotericin B, indicating their potential as candidates for in vivo studies. Therefore, the aim of the present study was to evaluate the in vivo antileishmanial activity of the indazole derivatives NV6 and NV16. Methods: The compounds were administered intralesionally at concentrations of 10 and 5 mg/kg in a BALB/c mouse model of cutaneous leishmaniasis caused by Leishmania amazonensis. To evaluate the efficacy of the compounds, indicators such as lesion size, ulcer area, lesion weight, and parasitic load were determined. Amphotericin B was used as a positive control. Results: The compound NV6 showed leishmanicidal activity comparable to that observed with amphotericin B, with a significant reduction in lesion development and parasite load, while NV16 caused a reduction in ulcer area. Conclusions: These results provide strong evidence for the antileishmanial activity of NV6 and support future studies to improve its pharmacokinetic profile, as well as the investigation of combination therapies with other chemotherapeutic agents currently in use. Full article

Restricting the use of chemical pesticides in forestry requires the search for alternative solutions. These could be volatile organic compounds produced by three investigated species of bacteria (Bacillus amyloliquefaciens (ex Fukumoto) Priest, B. subtilis (Ehrenberg) Cohn and B. thuringiensis Berliner), which inhibit the growth of the pathogen F. oxysporum Schltdl. emend. Snyder & Hansen in forest nurseries. The highest inhibition of fungal growth (70%) was observed with B. amyloliquefaciens after 24 h of antagonism test, which had a higher content of carbonyl compounds (46.83 ± 8.41%) than B. subtilis (41.50 ± 6.45%) or B. thuringiensis (34.62 ± 4.77%). Only in the volatile emissions of B. amyloliquefaciens were 3-hydroxybutan-2-one, undecan-2-one, dodecan-5-one and tetradecan-5-one found. In contrast, the main components of the volatile emissions of F. oxysporum were chlorinated derivatives of benzaldehyde (e.g., 3,5-dichloro-4-methoxybenzaldehyde) and chlorinated derivatives of benzene (e.g., 1,4-dichloro-2,5-dimethoxybenzene), as well as carbonyl compounds (e.g., benzaldehyde) and alcohols (e.g., benzyl alcohol). Further compounds were found in the interactions between B. amyloliquefaciens and F. oxysporum (e.g., $\alpha$-cubebene, linalool, undecan-2-ol, decan-2-one and 2,6-dichloroanisole). Specific substances were found for B. amyloliquefaciens (limonene, nonan-2-ol, phenethyl alcohol, heptan-2-one and tridecan-2-one) and for F. oxysporum (propan-1-ol, propan-2-ol, heptan-2-one and tridecan-2-one). The amounts of volatile chemical compounds found in B. amyloliquefaciens or in the bacterium–fungus interaction can be used for further research to limit the pathogenic fungus. In the future, one should focus on the compounds that were found exclusively in interactions and whose content was higher than in isolated bacteria. In order to conquer an ecological niche, bacteria increase the production of secondary metabolites, including specific chemical compounds. The results presented are a prerequisite for creating an alternative solution or supplementing the currently used methods of plant protection against F. oxysporum. Understanding and applying the volatile organic compounds produced by bacteria can complement chemical plant protection against the pathogen, especially in greenhouses or tunnels where plants grow in conditions that favour fungal growth. Full article

The holistic use of Moringa oleifera Lam. seeds is not as popular amongst rural South Africans. This study screened for the phytochemicals, antimicrobial, and antioxidant potentials as well identifying the compounds in the oils of South African Moringa seed oils using cost-effective thin layer chromatography bioautography and dot blot assays, because fewer studies have been conducted using seed samples from this country. The results obtained indicated that the best oil extract yield (24.04%) was obtained for hexane from 60.10 g of powdered seeds. The yield of the other extracts ranged from 6.2 to 9.5%. Positive test results were obtained for terpenoids, steroids, alkaloids, flavonoids, phenols, and tannins, with potentially good antioxidant properties for scavenging free radicals from 2,2-diphenyl-1-picrylhydrazyl (DPPH) and good antimicrobial activity against Acinetobacter baumannii (BAA 747), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 27853), and Pseudomonas aeruginosa (ATCC 27853), with the best zone of inhibition of 314.2 mm² obtained for oil extracted with hexane, followed by dichloromethane, methanol, and acetone oil extracts, respectively. The best minimum inhibitory concentration (MIC) of 0.032 mg/mL against P. aeruginosa was recorded for the hexane oil, compared with ciprofloxacin, which had an MIC of 0.0039 mg/mL against the same pathogen. The identification of the in-oil compounds proposed to mitigate inhibitory activity against the test microbes was carried out through GC-MS analysis matching our results with the GC-MS library. These compounds included ursane-3,16-diol, azetidin-2-one, 1-benzyl-4à-methyl, dibutyl phthalate, 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene, 1H-pyrrole-2,5-dione, 3-ethyl-4-methyl, octopamine rhodoxanthin, 29,30-dinorgammacerane-3,22-diol, 21,21-dimethy, cholan-24-oic acid, 3,7-dioxo, and benzyl alcohol. These are in addition to the stability-indicating marker compounds like oleic acid (54.9%), 9-Octadecenoic acid (z)-, methyl ester (23.3%), n-hexadecanoic acid (9.68%), among others observed over a five year period. Full article

Heterocycles—cyclic compounds containing at least one non-carbon heteroatom (e.g., N, O, S)—are fundamental in medicinal chemistry due to their influence on a drug’s physicochemical and biological properties. They improve solubility, bioavailability, and facilitate molecular recognition through their electronic and hydrogen-bonding features. These properties make them indispensable in drug design. This study focuses on the synthesis of a key heterocyclic intermediate: benzyl-N-[4-(2-hydroxyethyl)-1,3-thiazol-2-yl]carbamate. This molecule incorporates a thiazole ring, known for its rigidity and electronic properties, that enhances target interactions. The 2-position bears a Cbz-protected amine, enabling orthogonal deprotection, while the 4-position features a hydroxyethyl side chain, providing a handle for further chemical modifications via nucleophilic substitution. Herein, we report the successful synthesis of this intermediate along with its full ¹H and ¹³C NMR spectra, melting point, and crystal structure, confirming its identity and purity. Full article

Traditional covalently cross-linked solid-state electrolytes exhibit desirable mechanical durability but suffer from limited processability and recyclability due to their permanent network structures. Incorporating dynamic covalent bonds offers a promising solution to these challenges. In this study, we report a reprocessable and recyclable polymer electrolyte based on a dynamic ester bond network, synthesized from commercially available materials. Polyethylene glycol diglycidyl ether (PEGDE) and glutaric anhydride (GA) were cross-linked and cured in the presence of benzyl dimethylamine (BDMA), forming an ester-rich polymer backbone. Subsequently, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was introduced as a transesterification catalyst to facilitate network rearrangement. Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) was incorporated to establish efficient ion transport pathways. By tuning the cross-linking density and catalyst ratio, the electrolyte achieved an ionic conductivity of 1.89 × 10⁻⁵ S/cm at room temperature along with excellent reprocessability. Full article

A series of eleven new N-alkyl 3-(3-benzyloxyquinoxalin-2-yl) propanamides were prepared based on the azide coupling of 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide with a variety of primary and secondary amines and the consequent conjunction of a broad spectrum of lipophile and hydrophile characters to a quinoxaline ring system. 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide was produced in a two-step reaction of methyl 3-(3-oxo-3,4-dihydroquinoxalin-2-yl) propanoate with benzyl chloride followed by the hydrazinolysis of the corresponding ester. The antiproliferative activity of the compounds was tested in various cancer cell lines, including PC-3, Hela, HCT-116, and MCF-7; they showed a wide spectrum of activity for most of the tested compounds. Compound 6k exhibited the highest activity, which was comparable to that of doxorubicin, with IC₅₀ (µM) values of 12.17 ± 0.9, 9.46 ± 0.7, 10.88 ± 0.8, and 6.93 ± 0.4 µM compared to 8.87 ± 0.6, 5.57 ± 0.4, 5.23 ± 0.3, and 4.17 ± 0.2 µM for doxorubicin against Hela, HCT-116, and MCF-7, respectively. The in silico mechanistic study revealed the inhibition of HDAC-6 through the binding of the unique zinc finger ubiquitin-binding domain (HDAC6 Zf-UBD). The docking results showed a specific binding pattern that emphasized the crucial role of the quinoxaline ring and its substituents. The newly developed derivatives were evaluated for antitumor effects against four cancer cell lines PC-3, HeLa, HCT-116, and MCF-7. This research led to the identification of a quinoxaline-based scaffold exhibiting broad-spectrum antiproliferative activity and a distinct mechanism involving binding to HDAC6 Zf-UBD. The findings highlight its potential for further optimization and preclinical studies to support future anticancer drug development. Full article

The integration of HS-SPME-GC/MS and UPLC-MS/MS techniques enabled the profiling of volatile organic compounds (VOCs) and amino acids (AAs) in 18 crabapple flower cultivars, facilitating the development of a novel VOC–AA model. Among the 51 identified VOCs, benzyl alcohol, benzaldehyde, and ethyl benzoate were predominant, categorizing cultivars into fruit-almond, fruit-sweet, and mixed types. The amino acids, namely glutamic acid (Glu), asparagine (Asn), aspartic acid (Asp), serine (Ser), and alanine (Ala) constituted 83.6% of the total AAs identified. Notably, specific amino acids showed positive correlations with key VOCs, suggesting a metabolic regulatory mechanism. The Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model, when combined with volatile organic compounds (VOCs) and amino acid profiles, enabled more effective aroma type classification, providing a robust foundation for further studies on aroma mechanisms and targeted breeding. Full article

Japanese sake, a traditional alcoholic beverage, contains several organic acids that may contribute to its sour taste. To identify these, a precolumn derivatization reagent, benzyl 5-(2-aminoethyl)-3-methyl-4-oxoimidazolidine-1-carboxylate (CIM-C₂-NH₂), developed for labeling carboxyl groups, was synthesized and applied to liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis of organic acids in six commercial sake samples. The majority primarily contained lactic acid (LA), and dicarboxylic acids, such as succinic acid (SA), malic acid (MA), and citramalic acid (CMA). The organic acid concentrations and compositions in the sake differed among brands. Notably, both l- and d-forms of LA were detected in all samples, while only d-CMA was present. To estimate the total acidic content, neutralization titration with sodium hydroxide was performed. In four of the six samples, titration results closely matched LC-MS/MS data, suggesting that l-LA, d-LA, SA, MA, and d-CMA were the primary contributors for the sour taste in these sakes. The discrepancy between titration and LC-MS/MS data for the other samples was attributed to the presence of other organic acids, which will be investigated in future studies. Full article

A reliable synthetic method based on the already known Blanc–Quelet methodology has been developed for upgrading bio-based phenols into valuable electrophilic mono-, di-, and trifunctional benzyl chlorides. These compounds show significant potential as building blocks for polymer production and the synthesis of specialty chemicals. As an example of their applicability, their direct interaction with formamide has been evaluated, obtaining an effective transformation towards the corresponding N-formylamides. These compounds represent versatile synthetic precursors to a variety of functionalized targets. Full article