Search Results (65)

Metal chelation to bioactive small molecules is a well-established strategy to enhance the biological activity of the resulting complexes. Among the widely explored structural motifs, the combination of prominent metal centers with naturally inspired derivatives has attracted considerable attention. One such promising platform is the flavone scaffold, derived from flavonoids and studied since ancient times. Flavones are plant-derived compounds known for their diverse biological activities and health benefits. They exhibit significant structural variability, primarily through backbone modifications such as hydroxylation. Importantly, coordination of metal ions to hydroxylated flavone cores often improves their natural bioactivities, including anticancer and antimicrobial effects. In this review, we summarize transition metal complexes incorporating hydroxyflavone (OH–F) ligands reported over the past 15 years. We provide a concise overview of synthetic approaches and structural characterization, with a particular emphasis on coordination modes (e.g., maltol-type, acetylacetonate-type, catechol-type, and others). Furthermore, we discuss biological evaluation results, especially anticancer and antimicrobial studies, to highlight the therapeutic potential of these complexes. Finally, we suggest directions for the future development of metal-based agents bearing hydroxyflavone moieties through several critical points in terms of the accuracy, reproducibility, and relevance of biological studies involving metal-based compounds. Full article

Flavone derivatives have emerged as promising antiviral agents, with baicalein demonstrating the potent inhibition of the SARS-CoV-2 main protease (Mpro). In this study, the unique electronic and structural properties of 3-hydroxyflavone (3-HF) were investigated using the density functional theory (B3PW91/cc-pVTZ), providing insights into its potential as a bioactive scaffold. Among mono-hydroxyflavone (n-HF) isomers, 3-HF exhibits an extensive intramolecular hydrogen-bonding network linking the phenyl B-ring to the A- and γ-pyrone C-rings, enabled by the distinctive C3-OH substitution. Despite a slight non-planarity (dihedral angle: 15.4°), this hydrogen-bonding network enhances rigidity and influences the electronic environment. A ¹³C-NMR chemical shift analysis revealed pronounced quantum mechanical effects of the C3-OH group, diverging from the trends observed in other flavones. A natural bond orbital (NBO) analysis highlighted an unusual charge distribution, with predominantly positive charges on the γ-pyrone C-ring carbons, in contrast to the typical negative charges in flavones. These effects impact C1s orbital energies, suggesting that the electronic structure plays a more significant role in ¹³C-NMR shifts than simple ring assignments. Given the established antiviral activity of hydroxylated flavones, the distinct electronic properties of 3-HF may enhance its interaction with SARS-CoV-2 Mpro, making it a potential candidate for further investigation. This study underscores the importance of quantum mechanical methods in elucidating the structure–activity relationships of flavones and highlights 3-HF as a promising scaffold for future antiviral drug development. Full article

Chemotherapy is a common treatment method for cancer that is often associated with strong side effects. To reduce these, research on extracts from medicinal plants and their active ingredients has been conducted. Although sea buckthorn (Hippophae rhamnoides) is a well-established medicinal plant, little is known about the chemical components responsible for its putative anticancer activity. This study focuses on both chemical and medical analyses of methanolic sea buckthorn root extracts. Cell viability measurements were performed on head and neck cancer cell lines, as well as non-tumorigenic control cells. Microwave and classical extractions under reflux were used to prepare the methanolic extracts. LC/MS and NMR were used to determine the structures of the molecules contained within these extracts. The aqueous phase of one sea buckthorn root extract reduced the viability of cancer cells, whereas the viability of non-tumorigenic control cells remained unaltered. The cell cycle phases of cancer cells treated with the extract shifted in comparison to control treatment. After 24 h, the number of cells in proliferative phases had increased. Two fractions of the extract that evoked alterations were identified. After a 48 h treatment, one of the fractions showed a higher number of apoptotic cells than the control. LC/MS and NMR analyses were conducted to attempt to identify the active compounds. We propose that the bioactivity of this extract is caused by a mixture of 2′-hydroxyflavone isomers. Full article

A characteristic of Chronic Obstructive Pulmonary Disease (COPD) is the inflammation of the respiratory pathway. Inflammatory regulators affected in COPD include cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), interleukin (IL-1β), and interleukin-6 (IL-6). Therefore, this systematic review aimed to investigate the biological activity of Indonesian medicinal plants as anti-inflammation through in vitro, in silico, and in vivo studies. A digital search was conducted using Scopus, Google Scholar, and PubMed online databases to find relevant articles by applying specific keywords related to the subject of interest. The results showed 18 studies that reported five Indonesian medicinal plants proven to inhibit inflammation regulation. The five plants were sambiloto (Andrographis paniculata), legetan warak (Adenostemma lavenia), kersen (Muntingia calabura), babadotan (Ageratum conyzoides), and sembung rambat (Mikania micrantha Kunth). In vitro studies, A. paniculata, A. lavenia, and M. calabura can suppress the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, in LPS-stimulated RAW 264.7 cells. In silico studies, compounds that have strong binding to bind inflammatory receptors are andrographiside contained in A. paniculata; ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid contained in A. lavenia; 7-Hydroxyflavone contained in M. calabura; and 22,23-Dihydrospinasterol contained in A. conyzoides. In vivo studies, extracts of A. paniculata, M. calabura, A. conyzoides, and M. calabura can reduce inflammation in lung tissue in animal models (hamsters, mice, and rats). This systematic review might help to develop COPD treatment and build scientifically natural products from Indonesian medicinal plants for future investigations. Full article

Excited state intramolecular proton transfer (ESIPT) within molecules in solvents plays important roles in photo-chemistry and photo-biology. Herein, the influence of 1-ethyl-3-methyl-imidazolium bis (trifluoromethylsulfonyl) imide ([EMIm][NTf₂]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm][PF₆]) on the ESIPT of 4′-N,N-diethylamino-3-hydroxyflavone (DEAHF) was explored. The density functional theory and time-dependent density functional theory methodologies were used. The calculated fluorescence spectrum reveals that the fluorescence peaks of DEAHF in [EMIm][NTf₂] and [BMIm][PF₆] originate from the emission of N* and T* forms. The structure’s optimization, infrared spectra, non-covalent interactions and the scanning of potential energy curves collectively demonstrate that the ESIPT of DEAHF likely happen more in [EMIm][NTf₂] than in [BMIm][PF₆]. The solvation effects in [BMIm][PF₆] exhibit greater prominence compared to those in [EMIm][NTf₂], as evidenced by the free energy curve. The alterations in dipole moment indicate a substantial solvation relaxation during the ESIPT processes. Our aforementioned research offers backing for the advancement of novel fluorescent probes. Full article

(1) Background: The onset of inflammation and oxidative stress after biomaterial implantation can lead to complications and prolonged recovery times. To address this, bioactive mesoporous glasses doped with cerium (0, 3.6 and 5.3 mol%) were loaded with three different biomolecules—3-hydroxyflavone, quercetin and morin hydrate—to enhance antioxidant properties while preserving bioactivity. (2) Methods: Elemental analysis, specific surface area determination, spectroscopic techniques, evaluation of antioxidant activity and in vitro bioactivity assessment were performed to characterize mesoporous glass loaded with biomolecules. (3) Results: Biomolecule loading gives values in the range of 0.5–2.0% and 10.3–39.6% for loading content and loading efficiency, respectively. The loading order is quercetin > morine hydrate > 3-hydroxyflavone, and a cerium percentage of 3.6 seems to be a good compromise. The antioxidant properties evaluated on both solids and solutions in contact with simulated biological fluids improve markedly over loaded glasses, and the most promising results are obtained with quercetin. In the most efficient systems, the bioactivity results were delayed and more evident at longer times (168 h) but were still retained. (4) Conclusions: We obtained new materials still bioactive with improved antioxidant properties that can be proposed for the regeneration of both hard and soft tissues. Full article

The regioselective glycosylation and product specificity of hydroxyflavonoid compounds profoundly influences their biological activity and stability, offering significant therapeutic potential. However, most cyclodextrin glucosyltransferases (CGTases) inherently lack regioselectivity and product specificity for flavone glycosylation. Herein, a CGTase from Paenibacillus macerans was engineered for enhanced glycosylation regioselectivity and product specificity by combining molecular docking analysis and saturation mutagenesis strategies. K232L (favoring 4′-and 6-hydroxyflavones) and K232V (favoring 7-hydroxyflavone) were identified with distinct preferences. In addition, H233Y (preferring for 4′-hydroxyflavones), H233T (preferring for 6′-hydroxyflavones), and H233K (preferring for 7′-hydroxyflavones) also demonstrated distinct regioselectivity. These variants further exhibited enhanced hydrolytic activity, enabling the efficient production of short sugar-chain glycosides. Molecular dynamics (MDs) simulations revealed that the variants adopted optimized catalytic conformations with increased loop region flexibility near the binding pocket, enhancing substrate accessibility. These findings underscore the pivotal roles of K232 and H233 in broadening the substrate scope of CGTase and offer valuable guidance for enzyme engineering targeting regioselective glycosylation. Full article

The reaction of 2-(1H-pyrrol-1-yl)ethanol with 3-hydroxyflavone in the presence of copper(II) bromide yielded a dimeric copper(II) complex, [μ-O-(κ²-O,O-flav)(κ²-N,O-2PEO)Cu]₂ (1) (flav = 3-hydroxyflavonolate; 2PEO = 2-(1H-pyrrol-1-yl)ethanolate) with both the flav and 2PEO ligands bound to the copper(II) atom in a κ²-bonding mode. The dimer is held electrostatically by bridging oxygen atoms between two copper atoms. Complex 1 was characterized by single-crystal X-ray diffraction, infrared, and UV-Vis spectroscopy, elemental analysis, and melting point determination. The complex crystallizes in the monoclinic space group P2₁/n (14) with cell values of a = 11.85340(10) Å, b = 8.51480(10) Å, c = 23.8453(2) Å; β = 99.3920(10)°. Full article

Anethum graveolens is an aromatic plant traditionally used as an antispasmodic and carminative. The objective of this study is to analyze the chemical composition of the essential oils and extracts obtained from seeds gathered in Errachidia, southern Morocco. Additionally, the antioxidant and antimicrobial properties of these oils and extracts will be evaluated. GC-MS analysis of the EO isolated by hydrodistillation revealed that its main compounds were E-anethole (38.13%), estragole (29.32%), fenchone (17.21%), and α-pinene (7.37%). The phenolic components were extracted using the methods of decoction and Soxhlet. The assay of the phenolic compounds showed that A. graveolens seeds contained considerable amounts of polyphenols, flavonoids, and condensed tannins, with variable levels depending on the extract analyzed. HPLC/UV-ESI-MS analyses performed on the decoction revealed a structural diversity of the molecules present in this extract, the most important of which were umbelliferone (12.35%), 3-hydroxyflavone (11.23%), rosmanol (8.95%), biotin (8.36%), emmotin H (4.91%), and coumarin (4.21%). The antioxidant activity, as determined by three techniques (DPPH•, FRAP, and CAT), demonstrated that the essential oils (EOs) and extracts had a potent capacity to counteract detrimental free radicals, control the generation of reactive oxygen species, and mitigate oxidative damages. The antimicrobial activity of the Eos and extracts was carried out in a liquid medium against five strains (E. cloacae, K. pneumoniae, E. coli, S. aureus, and S. epidermidis) and four candidiasis (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis) and Aspergillus niger. The results showed the effectiveness of the EOs compared to the aqueous, ethanolic, and decoction extracts against most of the microorganisms tested. In addition, the ethanolic extract showed antifungal activity that was distinguished from that of the other extracts. The antimicrobial efficacy of the essential oils under study can primarily be attributed to the synergistic interactions among its three principal constituents (E-anethole, estragole, and fenchone). Furthermore, molecular docking and molecular dynamics simulation results reveal significant interactions and stability between the selected bioactive compounds and different target proteins involved in antimicrobial and antioxidant activities. Compounds like 3-hydroxyflavone, emmotin H, trans-caftaric acid, methyl rosmarinate, 1-caffeoyl-beta-D-glucose, and kaempferol exhibited better binding energies with the explored proteins, indicating their potential as antimicrobial and antioxidant agents. Finally, our findings emphasize the significance of A. graveolens seeds as a promising reservoir of advantageous health compounds that can serve as organic substitutes for the presently employed synthetic preservatives. Full article

In the present study, the complexes of aluminum and gallium with 5-hydroxyflavone were evaluated for their interaction with cyclodextrin polymers, as well as for the pharmacological effect of their inclusion. The cyclodextrin polymers were synthesized using diphenylcarbonate as a crosslinking agent, resulting in a lipophilic nanosponge (DPCNS), and pyromellitic dianhydride, resulting in a hydrophilic polymer (PMDACD). The inclusion complexes were synthesized and characterized via IR spectrometry and thermal analysis. The effect on the solubility of the metal complexes was also studied, where the hydrophobic nanosponge did not lead to an increase in solubility, but on the contrary, in the case of Al, it decreased; meanwhile, in the case of the hydrophilic polymer, the solubility of the metal complexes increased with the amount of polymer added. The cytostatic effect of inclusion complexes was investigated on two cell lines with different localizations, human colon adenocarcinoma (LoVo) and human ovarian adenocarcinoma (SKOV-3). The cytostatic efficacy is increased compared to simple complexes with efficacy on LoVo cells. Compared between the two metals, gallium complexes proved to be more active, with the efficacy of gallium complexes with the PMDACD being approximately the same as that of cisplatin, an antitumor agent used in therapy. Full article

The brain-derived neurotrophic factor (BDNF) plays a crucial role during neuronal development as well as during differentiation and synaptogenesis. They are important proteins present in the brain that support neuronal health and protect the neurons from detrimental signals. The results from the present study suggest BDNF expression can be increase up to ~8-fold by treating the neuroblastoma cells SHSY-5Y with an herbal extract of Oroxylum indicum (50 μg/mL) and ~5.5-fold under lipopolysaccharides (LPS)-induced inflammation conditions. The Oroxylum indicum extract (Sabroxy) was standardized to 10% oroxylin A, 6% chrysin, and 15% baicalein. In addition, Sabroxy has shown to possess antioxidant activity that could decrease the damage caused by the exacerbation of radicals during neurodegeneration. A mode of action of over expression of BDNF with and without inflammation is proposed for the Oroxylum indicum extract, where the three major hydroxyflavones exert their effects through additive or synergistic effects via five possible targets including GABA, Adenoside A2A and estrogen receptor bindings, anti-inflammatory effects, and reduced mitochondrial ROS production. Full article

Naodesheng Tablet (Naodesheng Pian), a traditional Chinese medicine formula for stroke treatment, is made up of five herbal medicines, i.e., Sanqi, Gegen, Honghua, Shanzha, and Chuanxiong. However, the current Pharmacopoeia quality-marker (Q-marker) system cannot detect possible adulteration. Our study tried to use a new strategy, i.e., standards-library-dependent ultra-high-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS/MS) putative identification, to reconstruct the Q-marker system. Through the strategy, 30 isomers were successfully differentiated (such as 2′-hydroxygenistein, luteolin, and kaempferol; ginsenoside Rg2 and ginsenoside Rg3; ginsenoside Rf and ginsenoside Rg1). In particular, 11 compounds were unexpectedly found in Naodesheng, including 2′-hydroxygenistein, 7,4′-dihydroxyflavone, pectolinarigenin, 7-methoxy-4′-hydroxyisoflavone, scoparone, matrine, 3,3′,4′,5,6,7,8-heptamethoxyflavone, 5-hydroxyflavone, diosgenin, chloesteryl acetate, and (+)-4-cholesten-3-one. In total, 68 compounds were putatively identified and fully elucidated for their MS spectra. Subsequently, relevant compounds were further investigated using UV-vis scanning experiments, semi-quantitative analysis, and quantum chemical calculation. Finally, five adulterated Naodesheng Tablets were used for validation experiments. The experiment successfully detected five adulterated ones via a lower-version LC-MS analysis. On this basis, three new candidates (hydroxy safflor yellow A (HSYA), citric acid, and levistilide A), along with puerarin and notoginsenoside R1, are re-nominated as the Q-markers for LC-MS analysis. The LC-MS analysis of puerarin, notoginsenoside R1, HSYA, citric acid, and levistilide A can clearly detect adulteration regarding all five herbal medicines mentioned above. Therefore, the reconstructed Q-markers are described as a “perfect” quality control system to detect adulteration in Naodesheng and will offer a valuable recommendation for the Pharmacopoeia Commission. Full article

During the synthetic studies toward 5,6,7,3′,4′-monomethoxytetrahydroxyflavones, a concise pedalitin synthesis procedure was achieved. As previously reported, 6-hydroxy-2,3,4-trimethoxyacetophenone was prepared by Friedel–Crafts acylation of 1,4-dihydroxy-2,6-dimethoxybenzene with boron trifluoride diethyl etherate in acetic acid. When aldol condensation of 6-hydroxy-2,3,4-trimethoxyacetophenone 2b with vanillin was performed in basic conditions, it produced 2′-hydroxychalcone 3b, and, surprisingly, along with 3-hydroxyflavone 4 in a considerable amount. We propose that this oxidative cyclization is presumably due to the contribution of a quinone methide, likely to be subjected to aerobic oxidation. The chalcone was then subjected to oxidative cyclization with iodine in dimethyl sulfoxide to afford flavone 5 in good yield. To our delight, serial demethylation of the three methoxy groups at the 5-, 6-, and 3′-positions of 5 proceeded smoothly to produce pedalitin 1, under hydrogen bromide solution (30% in acetic acid). The crystal structures of 3-hydroxyflavone 4 and pedalitin tetraacetate 6 were unambiguously determined by X-ray crystallography. Full article

Albertia edulis is known as Puruí, and its leaf tea is used in the hypoglycemic and antihypertensive treatments of the Amazon native population. This study aimed to evaluate the phytochemical composition and antioxidant properties of the Puruí pulp fruit. The hydroethanolic (LFP-E), ethyl acetate (LFP-A), and volatile concentrate (LPF-V) extracts of Puruí lyophilized fruit pulp were analyzed via LC-ISI-IT-MS, GC, and GC-MS. Moreover, total phenolic and flavonoid content (TPC and TFC) and TEAC/ABTS and DPPH assays were conducted to determine their antioxidant capacity. Compounds palmitic acid, methyl linolenate, methyl linoleate, palmitic alcohol, benzene acetaldehyde, tridecanal, and furfural were mainly identified in the LPF-V extract. Compounds caffeic and quinic acids, genipin, annonaine, 3′-7-dimethoxy-3-hydroxyflavone, 4′-hydroxy-5,7-dimethoxyflavone, 6-hydroxy-7-epigardoside methyl ester, baicalin, and phloretin-2-O-apiofuranosyl-glucopyranoside were mainly identified in the LFP-E and LFP-A extracts. For LFP-E and LFP-A extracts, TPC values were 5.75 ± 0.75 and 66.75 ± 3.1 mg GAE/g; TFC values were 1.14 ± 0.65 and 50.97 ± 1.2 mg QE/g; DPPH assay showed EC₅₀ values of 1021.65 ± 5.9 and 133.60 ± 3.9 µg/mL; and TEAC/ABTS assay showed values of 28.36 ± 3.7 and 142.26 ± 2.2 µM TE/g. Alibertia edulis fruits are significant sources of phenolic compounds, also showing significant antioxidant capacity. The Puruí fruit seems promising for developing innovative and healthy products for the nutritional food market. Full article

In this paper, an efficient synthetic route from pyrazole-chalcones to novel 6-aryl-5-hydroxy-2-phenylpyrano[2,3-c]pyrazol-4(2H)-ones as 3-hydroxyflavone analogues is described. The methylation of 5-hydroxy-2,6-phenylpyrano[2,3-c]pyrazol-4(2H)-one with methyl iodide in the presence of a base yielded a compound containing a 5-methoxy group, while the analogous reaction of 5-hydroxy-2-phenyl-6-(pyridin-4-yl)pyrano[2,3-c]pyrazol-4(2H)-one led to the zwitterionic 6-(N-methylpyridinium)pyrano[2,3-c]pyrazol derivative. The treatment of 5-hydroxy-2,6-phenylpyrano[2,3-c]pyrazol-4(2H)-one with triflic anhydride afforded a 5-trifloylsubstituted compound, which was further used in carbon–carbon bond forming Pd-catalyzed coupling reactions to yield 5-(hetero)aryl- and 5-carbo-functionalized pyrano[2,3-c]pyrazoles. The excited-state intramolecular proton transfer (ESIPT) reaction of 5-hydroxypyrano[2,3-c]pyrazoles from the 5-hydroxy moiety to the carbonyl group in polar protic, polar aprotic, and nonpolar solvents was observed, resulting in well-resolved two-band fluorescence. The structures of the novel heterocyclic compounds were confirmed by ¹H-, ¹³C-, ¹⁵N-, and ¹⁹F-NMR spectroscopy, HRMS, and single-crystal X-ray diffraction data. Full article