3-hydroxyflavone Research Articles

A high-contrast NIR excitation probe for monitoring Cu2+ in the endoplasmic reticulum for synergistic cuproptosis and ferroptosis anticancer therapy.

Currently, the study of cuproptosis focuses on the Cu2+-induced morphology changes in mitochondria (Mito), and the observation of the effect of endoplasmic reticulum (ER)-related Cu2+ content on cuproptosis is relatively lacking. Herein, we have developed a hydroxyflavone (HF)-based NIR excited two-photon fluorescent probe, BHCO, that exhibits specific recognition of Cu2+ with high resolution. BHCO-Cu2+ (Cu2BC) can lead to DLAT protein aggregation, triggering cuproptosis. Furthermore, Cu2BC can upregulate reactive oxygen species (ROS) under 720 nm excitation, which facilitates ferroptosis. The synergistic effect of ferroptosis and cuproptosis leads to the damage of cellular mitochondria and endoplasmic reticulum, resulting in the severe death of cancer cells. We are firmly convinced that our nonlinear optical (NLO) small molecule probe for monitoring Cu2+ could provide a valid tool for rapid tumor elimination through synergistic ferroptosis and cuproptosis.

An insight into the role of ESIPT/TICT-based antioxidant flavone analogues in fluoro-probing diabetes-induced viscosity changes: a unified experimental and theoretical endeavour.

Potent antioxidants, like 3-hydroxy flavones, attracted considerable attention due to their excited state intramolecular proton transfer (ESIPT)-based fluorescence behaviour. This article is an interesting demonstration of a series of synthetic 3-hydroxy flavone analogues having high antioxidant activity as molecular rotor-like viscosity probes. Among these flavone analogues, 4'-N,N-dimethylamino-3-hydroxy flavone (3) is the most potent one, showing the twisted intramolecular charge transfer (TICT)-dependent fluoroprobing activity toward the blood viscosity changes associated with diabetes and free fatty acids (FFA)-induced nuclear viscosity changes of MIN6 cells. The TICT dynamics of (3), which instigates its viscosity probing activity, was comprehended with the help of DFT-based computational studies. Abnormal cellular viscosity changes are the pathological traits for various diseases, and non-toxic flavone-based viscosity probes can be useful for diagnosing such pathological conditions.

Sonoinduced Tumor Therapy and Metastasis Inhibition by a Ruthenium Complex with Dual Action: Superoxide Anion Sensitization and Ligand Fracture.

Photoresponsive ruthenium(II) complexes have recently emerged as a promising tool for synergistic photodynamic therapy and chemotherapy in oncology, as well as for antimicrobial applications. However, the limited penetration power of photons prevents the treatment of deep-seated lesions. In this study, we introduce a sonoresponsive ruthenium complex capable of generating superoxide anion (O2•-) via type I process and initiating a ligand fracture process upon ultrasound triggering. Attaching hydroxyflavone (HF) as an "electron reservoir" to the octahedral-polypyridyl-ruthenium complex resulted in decreased highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gaps and triplet-state metal to ligand charge transfer (3MLCT) state energy (0.89 eV). This modification enhanced the generation of O2•- under therapeutic ultrasound irradiation at a frequency of 1 MHz. The produced O2•- rapidly induced an intramolecular cascade reaction and HF ligand fracture. As a proof-of-concept, we engineered the Ru complex into a metallopolymer platform (PolyRuHF), which could be activated by low-power ultrasound (1.5 W cm-2, 1.0 MHz, 50% duty cycle) within a centimeter range of tissue. This activation led to O2•- generation and the release of cytotoxic ruthenium complexes. Consequently, PolyRuHF induced cellular apoptosis and ferroptosis by causing mitochondrial dysfunction and excessive toxic lipid peroxidation. Furthermore, PolyRuHF effectively inhibited subcutaneous and orthotopic breast tumors and prevented lung metastasis by downregulating metastasis-related proteins in mice. This study introduces the first sonoresponsive ruthenium complex for sonodynamic therapy/sonoactivated chemotherapy, offering new avenues for deep tumor treatment.

Cu(II) flavonoids as potential photochemotherapeutic agents.

Flavonoids, naturally derived polyphenolic compounds, have received significant attention due to their remarkable biochemical properties that offer substantial health benefits to humans. In this work, a series of six Cu(II) flavonoid complexes of the formulation [Cu(L1)(L2)](ClO4) where L1 is 3-hydroxy flavone (HF1, 1 and 4), 4-fluoro-3-hydroxy flavone (HF2, 2 and 5), and 2,6-difluoro-3-hydroxy flavone (HF3, 3 and 6); L2 is 1,10-phenanthroline (phen, 1-3) and 2-(anthracen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip, 4-6) were successfully synthesized, fully characterized and also evaluated for their in vitro photo-triggered cytotoxicity in cancer cells. The single-crystal X-ray diffraction structure of complex 2 shows square pyramidal geometry around the Cu(II) center. The complexes 1-6 showed quasi-reversible cyclic voltammetric responses for the Cu(II)/Cu(I) couple at ∼-0.230 V with a very large ΔEp value of ∼350-480 mV against the Ag/AgCl reference electrode in DMF-0.1 M tetrabutylammonium perchlorate (TBAP) at a scan rate of 50 mV s-1. The complexes were found to have considerable binding propensity for human serum albumin (HSA) and calf thymus DNA (ct-DNA). The complexes displayed remarkable dose-dependent photocytotoxicity in visible light (400-700 nm) in both A549 (human lung cancer) and MCF-7 (human breast cancer) cell lines while remaining significantly less toxic in darkness. They were found to be much less toxic to HPL1D (immortalized human peripheral lung epithelial) normal cells compared to A549 and MCF-7 cancer cells. Upon exposure to visible light, they generate reactive oxygen species, which are thought to be the main contributors to the death of cancer cells. In the presence of visible light, the complexes predominantly elicit an apoptotic mode of cell death. Complex 6 preferentially localizes in the mitochondria of A549 cells.

HPLC/ESI-MS Characterization of Phenolic Compounds from Cnicus benedictus L. Roots: A Study of Antioxidant, Antibacterial, Anti-Inflammatory, and Anti-Alzheimer's Activity.

The phenolic composition of Cnicus benedictus roots from four Algerian regions was investigated. Extractions were performed in both hydro-methanolic (30 : 70, v/v) and hydro-ethanolic (30 : 70, v/v) solvents. Their efficiency was determined in terms of the qualitative and quantitative composition in phenolic compounds by HPLC-LC/MS of the different extracts isolated from C. Benedictus roots. Cnicus benedictus roots extract have been characterized by high content of phenolic compounds, where the trans chalcone, 2,3-dihydro flavone, 3-hydroxy flavone and cinnamic acid constitute the major components, in addition to fourteen minor acidic compounds and flavonoids as rutin. The hydro-methanolic extract was the richest in phenolic compounds yield from C benedictus. On the other hand, hydro methanolic (30 : 70, v/v) and hydro ethanolic (30 : 70, v/v) extracts exhibited a high anti-inflammatory activity by in vitro 5-lipoxygenase inhibitory activity (IC50 : 6.05±94.16 μg/mL) as well as by in silico docking according two methods. Likewise, anti-Alzheimer activity of extracts was confirmed by this last technique taking into account the major compounds identified. Antibacterial tests revealed interesting results compared to amoxicillin for the different regions studied with a high content in trans chalcone and 3-hydroxy Flavone.

Phytochemical Analysis and Allelopathic Effects of Quinoa (Chenopodium quinoa Willd.) Grain Extract M. Kadri, M., N. Salhi and A. Chana (ALGERIA)

Kadri, M., N. Salhi and A. Chana. 2023. Phytochemical Analysis and Allelopathic Effects of Quinoa (Chenopodium quinoa Willd.) Grain Extract. Arab Journal of Plant Protection, 41(3): 246-257. https://doi.org/10.22268/AJPP-41.3.246257 This study aimed to determine the phytochemical composition of Chenopodium quinoa extracts and to show their allelopathic effects on the seed germination of some plants such as wheat (Triticum durum L.), rapeseed (Brassica napus L.) and sugarbeet (Beta vulgaris L.). The results of the chemical screening revealed that quinoa grains contain flavonoids, alkaloids, tannins, reducing compounds, sterols and triterpenes, and they are rich in saponins. polyphenols and flavonoids were determined in both aqueous and methanolic extracts. The results of TLC chromatography showed the presence of flavonoids represented by flavonol and flavanols catechin, quercetin, flavanone or flavone and chalcone. HPLC analysis identified and determined content of catechin, acacetin, tangeretin, caffeic acid and 2,3,4,5,7 Penta hydroxy flavone in methanolic extracts. Nevertheless, aqueous extracts of Chenopodium quinoa Willd. inhibited germination of sugarbeet seeds by 72%, and stimulated root length and peduncle growth in wheat and rapeseed seeds. Keywords: Chenopodium quinoa, allelopathy, HPLC, polyphenol, flavonoid.

Structure-specific metabolism of flavonol molecules by Bacillus subtilis var. natto BCRC 80517

Flavonols (3-hydroxy flavones) have been studied for their beneficial bioactivities for human health. Recently, we reported that a flavonoid phosphate synthetase (BsFPS) from Bacillus subtilis BCRC 80517 can transform several flavonoids into their phosphate conjugates, which become more water-soluble and thus increase the oral bioavailability. However, the in vivo metabolism of different flavonols has yet to be determined. Here, we investigated biotransformation of three flavonols (quercetin, kaempferol and fisetin) by B. subtilis BCRC 80517. C-ring cleavage products of quercetin and kaempferol, i.e., 2-protocatechuoyl-phloroglucinol carboxylic acid (2-PCPGCA), were produced, whereas two phosphate derivatives of fisetin (fisetin 4′-O-phosphate and fisetin 3′-O-phosphate) were generated by cultivation with B. subtilis BCRC 80517. Our results indicated that there are structure-specific metabolic pathways in B. subtilis toward different flavonols, where the 5-hydroxy group determines metabolic priority. Our findings provide new insights for developing bioproduction platform to produce flavonol phosphate derivatives for nutraceutical applications.

Phytochemical study using HPLC-UV/GC–MS of different of Cannabis sativa L seeds extracts from Morocco

Within the framework of the valorization of cannabis seeds harvested in Ketama located in the region of Tangier-Tetouan-Al Hoceima, Morocco, a phytochemical study was carried out. The hexane extract of cannabis seeds was prepared and analyzed by gas chromatography-mass spectroscopy (GC–MS). The study proved that the natural extracts of Cannabis Sativa L seeds contain a variety of phenolic compounds to which various biological activities are attributed. Therefore, we have chosen to evaluate the quantitative estimation of total polyphenols (the Folin-Ciocalteu method) and subsequently the chemical composition of the different organic extracts by HPLC-UV. The quantitative analyses of total polyphenols determined that ethanolic and aqueous extracts were the richest with polyphenols compound. The results obtained by GC–MS reveal the presence of linoleic acid (omega 6) and 7- octadecenoic acid as main composition; first comes linoleic acid (omega 6) with 42.92% portion, followed by 7- octadecenoic acid with 22.91% portion respectively. Moreover, the analysis of the organic extracts by high-performance liquid chromatography revealed the probable presence of catechin di-hydrate, 6 hydroxy flavone, ferulic acid, 8 methoxy flavone, hesperidin acid, rutin and cinnamic acid in the dichloromethane extract, naringin acid was the main component in the ethanolic extract with a percentage of 41. 92% followed by rutin, hesperidin acid, O-dianisidine, ferulic acid, chlorogenic acid, coumarin, and cinnamic acid. On the other hand, aqueous extract was found to be rich in catechin di-hydrate, O. dianisidine, cinnamic acid, p-coumaric acid, caffeic acid, benzoic acid, and sinapinic acid.

Elucidation of possible mechanisms of the antidiabetic potential of Zn-loaded Bryophyllum pinnatum (Lam.) extracts in experimental animal models

BackgroundThe present study focused on the antidiabetic potential and fingerprinting analysis of Bryophyllumcpinnatum stems as well as its possible mechanisms of action along with identification of its major phytoconstituents. The oral glucose tolerance test has been performed administering a glucose solution (2000 mg/kg) to induce hyperglycemia. Diabetes have been instigated by single intra-peritoneal injection of streptozotocin (65 mg/kg).ResultsAlcohol and aqueous extracts were found to be safe up to a dose of 3000 mg/kg. Oral glucose tolerance test results showed significant reduction in fasting blood glucose level. Alcohol and aqueous extracts (200, 400 mg/kg b.w.) showed significant reduction in fasting blood glucose among all groups. Groups receiving zinc sulfate-loaded extracts showed a statistically significant reduction in low-density lipoproteins, triglycerides and total cholesterol levels and enhanced levels of high density lipoproteins. Fingerprinting analysis has been performed to identify the major phytoconstituents of flavonoid category morin, chrysin, and 6-hydroxy flavones, as well as iso-quercetin, hyperosides and terpenoids present in the extracts possess antidiabetic potential.ConclusionsBoth alcohol and aqueous extracts found to possess significant antidiabetic activity in diabetic rats. Zinc sulfate synergistically potentiates the antidiabetic potential of alcohol extract. Fingerprinting analysis revealed the presence of flavonoids such as morin, chrysin, and 6-hydroxy flavones, as well as iso-quercetin, hyperosides, and terpenoids. The possible mechanisms of antidiabetic activity have been elucidated, although further studies are required to give more elaborated mechanism on molecular basis.Graphical abstract

On the role of pH and temperature on ground – and excited – state proton transfer of hydroxyflavones in lipidic bilayers of lecithin

Absorption and emission monitoring of bioactive flavonols, Hydroxyflavones (HFs), (3-HF, 3,6-diHF and 3,7-diHF), to explore their microenvironments as a function of pH and temperature in lipidic bi-layers of lecithin (EYPC), have been studied. The influence of lipidic bi-layers on the − OH groups deprotonation of HFs with several distribution in the vicinity of the polar phosphate groups of EYPC when pH changed as well as the position of −OH groups in the HFs structure on the excited-state intramolecular proton transfer (ESIPT), have been studied by fluorescence spectroscopy. It was found that at physiological pH, EYPC leads to the increase of the quantum yield of Tautomer fluorescence for HFs with multiple −OH groups. There is a temperature-dependent difference in the ESIPT process which takes place in HFs/EYPC systems. The findings are relevant for in vivo and in vitro studies of the oxidative stress process which involves cell membranes, where HFs are used as sensitive fluorescence probes.

Anti-Cancer Effect of Novel Hydroxy Flavons on Human Cancer Cell In vitro and In silico

Anti-cancer effect of 7 hydroxy Favone and its derivatives were tested against human cancer cell lines such MCF-7 cell line using the in vitro by MTT assay in cancer cell lines. All the favones showed significant activity against all pathogens. 7-HF showed a maximum zone of inhibition against cancer cell lines. 7-try hydroxy flavones showed the lowest anti-cancer activity. And docking results shown as 7-HF has shown maximum docking -7.9, 7,8,3’-THF has -7.5 and 7,3’,4’ has -7.7. as per the results, 7 hydroxy flavone could be a possible source to obtain new and effective compounds to treat cancer.

Anti-Inflammatory Effect of Three Novel Hydroxy Flavones

Aim: The aim of the present study was to evaluate the anti-inflammatory effect of three 7-hydroxy flavone derivatives; 7-HF, 7,3’,4’-THF, and 7,8,3’-THF,
 Materials and Methods: The acute anti-inflammatory effect of 7-hydroxy flavones was the effect of 7-hydroxy flavones on certain mediators of pain and inflammation like cyclooxygenases (COX-1 and COX-2), and pro-inflammatory cytokines (IL-1b and TNF- were investigated by using in vitro tests.
 Results: The investigated 7hydroxy flavones produced a significant, the test compounds inhibited both the isoforms of cyclooxygenase, a higher degree of inhibition on COX-2 was evident. Concentration-dependent inhibition of other inflammatory cytokines like tumour necrosis factor-a and interleukin-1b was identified in the present study
 Conclusion: conclusion of the present study reveal the pain and anti-inflammatory action of the investigated 7hydroxy flavones. The inhibitory effects of 7hydroxy flavone on various pro-inflammatory cytokines provide evidence for the mechanism of action of these compounds against pain and inflammation.

Effect of Flavone Derivatives on Vincristine and Oxaliplatin Induced Peripheral Neuropathy in Mice

Introduction: Therapy with anticancer drugs like paclitaxel, platinum complexes and vincristine result in severe peripheral neuropathy. Very few treatment options are available to overcome this debilitating side effect. Flavone and its monohydroxy derivatives have been proved to possess anti-nociceptive and anti-inflammatory effects in animal models. Aim: To investigate flavone, 5-hydroxy flavone, 6-hydroxy flavone and 7-hydroxy flavone for their effect on neuropathy induced by vincristine and oxaliplatin in mice. Materials and Methods: In this experimental animal study, neuropathy was induced in mice by multiple doses of vincristine or a single dose of oxaliplatin. The manifestations of mechanical allodynia, cold allodynia and thermal hyperalgesia were measured by von Frey’s hair aesthesiometer, acetone spray test and hot water tail immersion test. The data was subjected to ANOVA followed by Dunnett’s test for multiple comparison and paired t-test at appropriate places. Results: Flavone and monohydroxy flavones significantly reduced the paw withdrawal response scores due to mechanical allodynia and cold allodynia resulting from vincristine or oxaliplatin administration (p<0.05). The tail withdrawal latency due to thermal hyperalgesia was also significantly increased by different flavone derivatives (p<0.05). However, 7-hydroxy flavone was ineffective in oxaliplatin-induced mechanical allodynia and vincristine induced thermal hyperalgesia. Analysis of the results indicated that the manifestations of neuropathy induced by vincristine or oxaliplatin were amenable to treatment with flavone derivatives in the following order; cold allodynia>thermal hyperalgesia>mechanical allodynia. Opioid mediated antinociceptive effect, interaction with cation channels and anti-inflammatory effect of the investigated flavones may be suggested as possible mechanisms for their beneficial effects in neuropathy due to chemotherapeutic agents. Conclusion: Various neuropathic manifestations induced by vincristine and oxaliplatin were effectively attenuated by flavone and monohydroxy flavones.

Biotransformation of Methoxyflavones by Selected Entomopathogenic Filamentous Fungi.

The synthesis and biotransformation of five flavones containing methoxy substituents in the B ring: 2′-, 3′-, 4′-methoxyflavones, 2′,5′-dimethoxyflavone and 3′,4′,5′-trimethoxyflavone are described. Strains of entomopathogenic filamentous fungi were used as biocatalysts. Five strains of the species Beauveria bassiana (KCh J1.5, J2.1, J3.2, J1, BBT), two of the species Beauveria caledonica (KCh J3.3, J3.4), one of Isaria fumosorosea (KCh J2) and one of Isaria farinosa (KCh KW 1.1) were investigated. Both the number and the place of attachment of the methoxy groups in the flavonoid structure influenced the biotransformation rate and the amount of nascent products. Based on the structures of products and semi-products, it can be concluded that their formation is the result of a cascading process. As a result of enzymes produced in the cells of the tested strains, the test compounds undergo progressive demethylation and/or hydroxylation and 4-O-methylglucosylation. Thirteen novel flavonoid 4-O-methylglucosides and five hydroxy flavones were isolated and identified.

Screening inhibitory effects of selected flavonoids on human recombinant aldose reductase enzyme: in vitro and in silico study

Aldose reductase (AR) is the first enzyme of the polyol pathway that has physiological importance under hyperglycaemic conditions. The article has been focussed on AR enzyme inhibition by selected compounds. For this purpose, the in vitro inhibitory effects of various compounds on commercially available recombinant human AR (rAR) enzyme activity were investigated. The IC50 values of compounds on rAR inhibition effect were found for 6-hydroxy flavone, syringic acid, diosmetin, 6-fluoroflavone, 7-hydroxy-4′-nitroisoflavone, myricetin as 2.05, 2.97, 15.75, 16.1, 49.5, and 63 µM, respectively. 6-Hydroxy flavone and syringic acid competitively inhibited rAR with respect to the NADPH with Ki values 0.509 ± 0.036 and 0.842 ± 0.012 µM. In addition, docking studies were performed to evaluate the potential enzyme binding positions of the compounds. Our in vitro and in silico results indicated that the 6-hydroxy flavone may be a good lead compound in the development of AR inhibitors to prevent diabetic complications.

Nematicidal activity of flavonoids with structure activity relationship (SAR) studies against root knot nematode Meloidogyne incognita

In continuation of our work on Tagetes spp., the current study deals with the nematicidal activity of flavonoids, which are structurally related to two marker compounds, patuletin and patulitrin isolated from Tagetes patula flowers. The activity was determined against root-knot nematode, Meloidogyne incognita to establish structure activity relationship. In vitro examination of flavonoids belonging to flavone and flavonol classes revealed significant differences in nematicidal ability depending on their structural motif, concentration, and time of exposure. In case of flavonols the most efficient compounds were found to be fisetin, galangin, isorhamnetin, morin, and myricetin which exhibited 100% mortality of 2nd stage juveniles after 24 h of incubation. Whereas, among flavones which showed the same excellent activity parameters, were simple flavone, 6-hydroxy flavone, chrysin, 6-methoxy apigenin, apigenin-7-O-glucoside and 6-methoxy luteolin. These results revealed that flavonoids possess promising nematicidal activity and may have potential use in crop management as active agents.

Colorimetric/naked eye detection of arsenic ions in aqueous medium by mango flower extract: A facile and novel approach

Laboratory-based instrumental methods are usually employed to detect arsenic with detection limit of 1 ppb. However, such detection methods are complex, difficult to operate, and expensive. Herein, a cost-effective, eco-friendly, and colorimetric/naked-eye detection technique for trace amount of arsenic present in water utilizing mango flower (Mangifera indica) extract (MFE) has been described. To the best of our knowledge, mango flower extract has been used for the first time for arsenic detection in water. The MFE was characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine its chemical composition. Detailed characterization and numerical analysis (Gaussian09 program) indicated that 3-hydroxy flavone and mangiferin present in MFE could be useful in detecting arsenic in natural water. The detection efficiency and selectivity of MFF towards several metal ion solutions at concentration of 1.0 mg l−1 was performed. It has been found that MFE was able to identify arsenic ions in various water samples with detection limit of ~200 ppb and linear range from ~200 to 2000 ppb at optimum conditions. Results of this study demonstrate that MFE could be useful to detect arsenic in groundwater without any significant installations.

Role of hydrogen in ground and excited state studies of 2-aryl-3-hydroxychromenones in different solvents

Radical scavenging activity (%SC) of three 2-heteroaryl 3-hydroxy chromenones (3-HCs) relative to 3-hydroxy flavones (3-HF) has been determined, using 2,2-diphenyl-1-picrylhydrazyl (DPPH) as a radical scavenger both in methanol (MeOH) and acetonitrile (ACN) as solvents. Among the three 3-HCs, 2-(furan-2-yl)-3-hydroxy-4 H-chromen-4-one (FHC), 3-hydroxy-2-(thiophene-2-yl)-4H-chromen-4-one (THC), and 3-hydroxy-2-(pyrrol-2-yl)-4H-chromen-4-one (PHC), the last 3-HC was included in our earlier reported studies on absorption, emission, and excitation spectra. Detailed studies on the excited state intramolecular proton transfer (ESIPT) on PHC relative to other three 3-HCs have been given. Order of %SCs is PHC > FHC > THC > 3-HF in MeOH and PHC > FHC ≈ THC > 3-HF in ACN, which are similar to that of intensity ratio of normal and tautomeric forms (IN*/IT*). Both %SC and IN*/IT* depend upon the potential of hydrogen of 3-hydroxy in 3-HCs in their ground and excited states, respectively. It has been found that for PHC, IN*/IT* and %SC are distinctly high compared with other chromenones. It is concluded that the determination of %SC can be as important as IN*/IT* for these.

Site-specific α-glycosylation of hydroxyflavones and hydroxyflavanones by amylosucrase from Deinococcus geothermalis

Amylosucrase (ASase) is a unique multifunctional enzyme exhibiting transglycosylation activity. In this study, the specificity of the transglycosylation activity of ASase was evaluated using several hydroxyflavones (HFVOs) and hydroxyflavanones (HFVAs). Our results reveal that the 3–OH and 7–OH positions of the mono-HFVOs and -HFVAs are resistant to transglycosylation by Deinococcus geothermalis ASase (DGAS), whereas the 6–OH and 4ʹ–OH positions of the mono-HFVOs and -HFVAs exhibit relatively strong transglycosylation reactivities with the glucose donors released from sucrose by DGAS. Particularly, the 6–OH position is considerably more reactive (54-fold higher kcat) than the 4ʹ–OH position in both HFVOs and HFVAs. Further, the transglycosylation reactions with di- and tri-HFVOs and HFVAs were also investigated and observed to exhibit similar results to those observed for the mono-HFVO and -HFVA molecules. The pH of the reaction influences the reactivity of certain hydroxyl residues, indicating that the pKa values of the hydroxyl groups may be crucial factors in the transglycosylation reactions. These observations help us understand the specificity of the transglycosylation activity of ASase and to predict the transglycosylation products of flavonoids.

Enhanced susceptibility to apoptosis and growth arrest of human breast carcinoma cells treated with silica nanoparticles loaded with monohydroxy flavone compounds.

The treatment of drug-resistant cancer is a clinical challenge, hence screening for novel anticancer drugs is critically important. In this study, we investigated the anti-tumor potential of three plant-derived flavone compounds: 3-hydroxy flavone (3-HF), 6-hydroxy flavone (6-HF), and 7-hydroxy flavone (7-HF), either alone or combined with silica nanoparticles (3-HF + NP, 6-HF + NP, and 7-HF + NP), on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of these flavone compounds loaded with NP (flavones + NP) in these cell lines were determined to be 1.5 μg/mL without affecting the viability of normal MCF-10 cells. Additionally, using annexin V - propidium iodide double-staining followed by flow cytometry analysis, we found that the combination of flavones with NP significantly induced apoptosis in MCF-7 and MDA-MB-231 cancer cells. Furthermore, flavones + NP increased the expression of cytochrome c and caspase-9, mediating the growth arrest of these cancer cells. Most importantly, the combination of flavones with NP significantly abolished the expression of ATF-3, which is responsible for the proliferation and invasion of bone-metastatic breast cancer cells. Our data revealed the potential therapeutic effects of these flavones in fighting breast cancer cells, and provide the first insights concerning the underlying molecular mechanisms.