54210-23-0

Upstream product

• 65786-14-3 (2E)-3-(4-bromophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one 
• 118-93-4 o-hydroxyacetophenone 
• 1122-91-4 4-bromo-benzaldehyde 
• 582-24-1 1-phenyl-2-hydroxyethanone 
• 13400-26-5 3-hydroxychromen-4-one 
• 622-88-8 4-bromophenylhydrazine hydrochloride 
• 65786-14-3 4-bromo-2'-hydroxylchalcone 
• 930-69-8 sodium thiophenolate 
• 81281-77-8 Methanesulfonic acid (2R,3R)-2-(4-bromo-phenyl)-4-oxo-chroman-3-yl ester 
• 17255-67-3 2-(4-bromophenyl)chroman-4-one 

Downstream Products

• 1413917-02-8 [chlorido{3-(oxo-κO)-2-(4-bromophenyl)-chromen-4-onato-κO}(η⁶-p-cymene)ruthenium(II)] 
• 1621102-00-8 4'-bromo-3-methoxyflavone 

Relevant academic research and scientific papers

Exploring 3-hydroxyflavone scaffolds as mushroom tyrosinase inhibitors: synthesis, X-ray crystallography, antimicrobial, fluorescence behaviour, structure-activity relationship and molecular modelling studies

To explore new scaffolds as tyrosinase enzyme inhibitors remain an interesting goal in the drug discovery and development. In due course and our approach to synthesize bioactive compounds, a series of varyingly substituted 3-hydroxyflavone derivatives (1-23) were synthesized in one-pot reaction and screened for in?vitro against mushroom tyrosinase enzyme. The structures of newly synthesized compounds were unambiguously corroborated by usual spectroscopic techniques (FTIR, UV-Vis, 1H-, 13C-NMR) and mass spectrometry (EI-MS). The structure of compound 15 was also characterized by X-ray diffraction analysis. Furthermore, the synthesized compounds (1-23) were evaluated for their antimicrobial potential. Biological studies exhibit pretty good activity against most of the bacterial-fungal strains and their activity is comparable to those of commercially available antibiotics i.e. Cefixime and Clotrimazole. Amongst the series, the compounds 2, 4, 5, 6, 7, 10, 11, 14 and 22 exhibited excellent inhibitory activity against tyrosinase, even better than standard compound. Remarkably, the compound 2 (IC50 = 0.280 ± 0.010 μg/ml) was found almost sixfold and derivative 5 (IC50 = 0.230 ± 0.020 μg/ml) about sevenfold more active as compared to standard Kojic acid (IC50 =1.79 ± 0.6 μg/ml). Moreover, these synthetic compounds (1-23) displayed good to moderate activities against tested bacterial and fungal strains. Their emission behavior was also investigated in order to know their potential as fluorescent probes. The molecular modelling simulations were also performed to explore their binding interactions with active sites of the tyrosinase enzyme. Limited structure-activity relationship was established to design and develop new tyrosinase inhibitors by employing 2-arylchromone as a structural core in the future. Communicated by Ramaswamy H. Sarma.

Synthesis of Flavonols via Pyrrolidine Catalysis: Origins of the Selectivity for Flavonol versus Aurone

A novel synthetic method for flavonol from 2′-hydroxyl acetophenone and benzaldehyde promoted by pyrrolidine under an aerobic condition in water is established. This protocol was supported by efficient synthesis of 44 common examples and three natural products. The α, β-unsaturated iminium ion (enimine ion E) was proved to be the key intermediate in the reaction. H218O and 18O2 isotope tracking experiments demonstrated that both water and the aerobic atmosphere were necessary to ensure the transformation. The selectivity for flavonol or aurone was originated from solvent-triggered intermediates, which were determined by UV-visible spectra from isolated enimine. The phenol-iminium E-A is dominant in water and the ketoenamine intermediate E-B is prevalent in acetonitrile. In the presence of pyrrolidine and oxygen, E-A leads to flavonol through E-I, a zwitterionic-like phenoloxyl-iminium ion, following the key steps of cyclization and a [2 + 2] oxidation; E-B proceeds through path II, a radical process induced by photolysis of E-B with both pyrrolidine and oxygen, to afford aurone. Preliminary mechanistic studies are reported.

Flavonol dyes with different substituents in photopolymerization

To further expand the applications of flavonol dyes (3HFs) in photopolymerization, six flavonol dyes with different substituents were prepared by using the Algar–Flynn–Oyamada method. The steady-state photolysis and fluorescence quenching of 3HFs under the 385 nm LED light source showed that the proton transfer reaction preceded the charge transfer reaction between 3HFs and triethanolamine (TEOA) or iodonium salts (ONI), and groups with different electron properties could affect the photochemistry of 3HFs. The influence of substituents on the free radical polymerization efficiencies of 3HFs/TEOA and 3HFs/ONI was evaluated. Results showed that charge transfer occurred in the oxidation or reduction processes between 3HFs and TEOA or ONI. The possible mechanism was speculated, and the thermal feasibility of charge transfer between 3HFs and TEOA or ONI was calculated on the basis of the free energy changes of photoinduced electron transfer.

Faster and More Specific: Excited-State Intramolecular Proton Transfer-Based Dyes for High-Fidelity Dynamic Imaging of Lipid Droplets within Cells and Tissues

Lipid droplets (LDs), a type of dynamic organelle residing at the center of cellular lipid storage, have been identified to play important roles in multiple biological processes, metabolic disorders, and diseases. The highly dynamic characters of LDs were found to correspond to their physiological and pathological functions. Hence, the fluorescent probes which enable dynamic tracking of LDs should be very helpful for better understanding the mechanisms of LDs involved biological processes and diseases. Herein we present, to the best of our knowledge, the first class of excited-state intramolecular proton transfer (ESIPT) fluorescence dyes (Flp-(11-13, 19)) for dynamic imaging of LDs based on 3-hydroxyflavone (3HF) derivatives. Flp-(11-13, 19) display strong fluorescence from yellow to NIR in lipid but exhibit almost nonfluorescence in aqueous solution. Besides, they also show large Stokes shifts (>150 nm), narrow absorption and emission peaks, and good oil-water separation efficiency, which makes them specifically target and stain LDs with very low background noisy in both living cells and fixed cells. They stain intracellular LDs quite quickly (within 30 s) with very low dosage (as low as 500 nM). Benefitting from these advantages, Flp-(11-13, 19) are applied successfully in tracking the dynamic nature of LDs and accumulation of LDs in both aqueous solution and living cells, 3D imaging of LDs for visualization of their repartition within the cells, and visualizing LDs in tissues of diseases mice models including adipose, skeletal muscle, and fatty liver tissues, underscoring the potential utility of these dyes in both LDs biology research and medical diagnosis of LDs involved diseases.

Alkynyl Gold(I) complexes derived from 3-hydroxyflavones as multi-targeted drugs against colon cancer

The design of multi-targeted drugs has gained considerable interest in the last decade thanks to their advantages in the treatment of different diseases, including cancer. The simultaneous inhibition of selected targets from cancerous cells to induce their death represents an attractive objective for the medicinal chemist in order to enhance the efficiency of chemotherapy. In the present work, several alkynyl gold(I) phosphane complexes derived from 3-hydroxyflavones active against three human cancer cell lines, colorectal adenocarcinoma Caco-2/TC7, breast adenocarcinoma MCF-7 and hepatocellular carcinoma HepG2, have been synthesized and characterized. Moreover, these compounds display high selective index values towards differentiated Caco-2 cells, which are considered as a model of non-cancerous cells. The antiproliferative effect of the most active complexes [Au(L2b)PPh3] (3b) and [Au(L2c)PTA] (4c) on Caco-2 cells, seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2 and alteration of the activities of the redox enzymes thioredoxin reductase and glutathione reductase. Both complexes triggered cell death by apoptosis, alterations in cell cycle progression and increased of ROS production. These results provide support for the suggestion that multi-targeting approach involving the interaction with cyclooxygenase-1/2 and the redox enzymes that increases ROS production, enhances cell death in vitro. All these results indicate that complexes [Au(L2b)PPh3] and [Au(L2c)PTA] are promising antiproliferative agents for further anticancer drug development.

Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis

Peptidyl-prolyl cis-trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7-(benzyloxy)-3,5-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4H-chromen-4-one (AF-39) was identified as a novel Pin1 inhibitor. Biochemical tests indicate that AF-39 potently inhibits Pin1 activity with an IC50 values of 1.008 μm, and also displays high selectivity for Pin1 among peptidyl prolyl isomerases. Furthermore, AF-39 significantly suppresses cell proliferation of HCC cells in a dose- and time-dependent manner. Mechanistically, AF-39 regulates the subcellular distribution of XPO5 and increases miRNAs biogenesis in HCC cells. This work provides a promising lead compound for HCC treatment, highlighting the therapeutic potential of miRNA-based therapy against human cancer.

Exploration of synthetic antioxidant flavonoid analogs as acetylcholinesterase inhibitors: an approach towards finding their quantitative structure–activity relationship

The binding interactions between acetylcholinesterase (AChE) and a series of antioxidant flavonoid analogs were studied by fluorescence spectroscopic assay. The present study incorporated different classes of naturally occurring and synthetic flavonoid compounds like flavones, isoflavones, and chalcones as well as a few standard antioxidants. The AChE inhibitory (AChEI) activity of these compounds was further analyzed using in silico techniques, namely pharmacophore mapping, quantitative structure–activity relationship (QSAR) analysis, and molecular docking studies. We have also compared the AChE inhibitory and radical scavenging antioxidant activities of these compounds. Both the AChE inhibitory and antioxidant activities of these compounds were found to be highly dependent on their structural patterns. However, it was observed that, in general, flavones are comparatively better AChE inhibitors as well as antioxidants compared to chalcones. [Figure not available: see fulltext.].

Hydroxyl directed: C -arylation: Synthesis of 3-hydroxyflavones and 2-phenyl-3-hydroxy pyran-4-ones under transition-metal free conditions

An efficient, transition-metal free and direct C-arylation of 3-hydroxychromone moieties in the presence of a base, air as an oxidant and arylhydrazines as arylating agents to furnish highly biologically active flavonols or 3-hydroxyflavones has been developed. We have further extended our methodology for the C-arylation of the 5-hydroxy pyran-4-one moiety. The role of the free hydroxyl group towards C-arylation has been delineated.

Synthesis, structure-activity relationship and molecular docking studies of 3-O-flavonol glycosides as cholinesterase inhibitors

The prime objective of this research work is to prepare readily soluble synthetic analogues of naturally occurring 3-O-flavonol glycosides and then investigate the influence of various substituents on biological properties of synthetic compounds. In this context, a series of varyingly substituted 3-O-flavonol glycosides have been designed, synthesized and characterized efficiently. The structures of synthetic molecules were unambiguously corroborated by IR, 1H, 13C NMR and ESI-MS spectroscopic techniques. The structure of compound 22 was also analyzed by X-ray diffraction analysis. All the synthetic compounds (21–30) were evaluated for in vitro inhibitory potential against cholinesterase enzymes. The results displayed that most of the derivatives were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with varying degree of IC50 values. The experimental results were further encouraged by molecular docking studies in order to explore their binding behavior with the active pocket of AChE and BChE enzymes. The experimental and theoretical results are in parallel with one another.

Pot-economic synthesis of diarylpyrazoles and pyrimidines involving Pd-catalyzed cross-coupling of 3-trifloxychromone and triarylbismuth

Abstract: The present study reveals the formation of 3,4-diarylpyrazole and 4,5-diarylpyrimidine in one-pot operation starting from 3-trifloxychromone and triarylbismuth. The complete process encompasses two steps in the one-pot operation. The first step leads to the formation of isoflavone via cross-coupling reaction of 3-trifloxychromone and triarylbismuth as a threefold arylating reagent. These isoflavones were further converted into 3,4-diarylpyrazole and 4,5-diarylpyrimidine using hydrazine hydrate and guanidinium chloride in the successive step in the same pot. Interestingly the formation of 3,4-diarylpyrazole was achieved in the shortest reaction time i.e., 30 min that too at room temperature. Overall the developed methodology provides easy access to the medicinally important diarylpyrazole and pyrimidine moiety in one-pot operation and in short reaction time. Graphical Abstract: Synopsis The work presented here describes the novel methodology for the formation of medicinally important heterocycles 3,4-diarylpyrazole and 4,5-diarylpyrimidine in one-pot operation starting from 3-trifloxychromone and triarylbismuth.