Hydroxy Chalcones Research Articles

Thermo-controlled Water Microenvironment Inducing Fluorescence Enhancement of Chalcone Nanohydrogels for Mitochondrial Temperature Sensing.

Developing aggregation-induced emission (AIE)-based hydrogels that exhibit fluorescence enhancement as to thermal properties is an interesting and challenging task. In this work, we employed the fluorophore 2'-hydroxychalcone (HC), fluorescence properties of which are easily influenced by the excited-state intramolecular proton transfer and twisted intramolecular charge transfer (TICT) effects, to develop a novel type of temperature-sensitive polymers, hydroxychalcone-based polymers (HCPs). By controlling the temperature-dependent water microenvironments in HCPs, the intramolecular hydrogen bonds between water and HCPs can be regulated, thereby influencing the TICT process and leading to thermo-induced fluorescence enhancement, which shows a contrary tendency compared to typical AIEgens that always exhibit fluorescence attenuation as the thermal energy accelerates the molecular motion. Following the decoration with triphenylphosphine, the resulting polymer P-HCP assembled into nanohydrogels and served as a fluorescent probe for intracellular mitochondrial temperature sensing.

Molecular Docking Analysis of Hydroxy Chalcones and Flavones from Anisaldehyde and Veratraldehyde as EGFR Inhibitors: Predicting Anticancer Potential

This study aimed to investigate the potential of hydroxy chalcone and flavone derivatives as inhibitors of the epidermal growth factor receptor (EGFR) with anticancer properties. Molecular docking simulations were conducted using Autodock Tools 1.5.6 and Discovery Studio visualizer. The EGFR protein structure with the PDB code 1M17 was utilized as the receptor, explicitly targeting the binding pocket. Redocking of the reference ligand erlotinib yielded a binding energy of -7.51 kcal mol-1 with an RMSD of 0.54 Å, confirming the accuracy of the docking protocol. The hydroxy chalcone and flavone derivatives exhibited binding energies ranging from -6.50 to -7.67 kcal mol-1 when interacting with the EGFR protein. Among the studied compounds, compound 2',5'-dihydroxy-3,4-dimethoxychalcone (1g) displayed the lowest binding energy. Interactions involving amino acids such as Met769, Ala719, Thr766, Lys721, and Glu738 were identified as crucial hydrogen bonding interactions between the ligands and the EGFR protein. These findings suggest that 2',5'-dihydroxy-3,4-dimethoxychalcone holds strong potential as a tyrosine kinase inhibitor, positioning it as a promising candidate for further development as an anticancer agent. The outcomes of the computational analysis conducted through the pkCSM online platform indicated that the chemical 2',5'-dihydroxy-3,4-dimethoxychalcone had favorable pharmacokinetic characteristics and showed low toxicity levels.
 
 Keywords: molecular docking, hydroxy chalcone, flavone, egfr, ADMET

Microwave-Accelerated Synthesis of Flavanones through Oxidative Cyclization of 2'-Hydroxychalcones Using Acetic Acid as a Sole Catalyst

Under microwave irradiation conditions, 2'-hydroxy chalcones 1a-c underwent AcOH-mediated cyclization in an oxa-Michael addition manner to afford flavanones 2a-c in acceptable yields (up to 82%). These reactions proceeded in a shorter reaction time (~ 30 min) through microwave activation; otherwise, the reaction would take several days and even weeks, if a conventional heating process was employed. For example, cyclization of (E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (1a) has required 4 days of stirring with AcOH (0.25 M), under conventional heating at 100 °C, to produce 2-phenylchroman-4-one (2a), in 75% yield; while under microwave conditions, the reaction has yielded 82% of compound 2a, after 30 min. Thus obtained products 2a-c were fully characterized by recording of melting point together with UV, 1H NMR, and 13C NMR spectra.

Optimization of Synthetic Condition for 2’hydroxy Chalcone by using Mixture Design

Chalcone derivatives are crucial compounds in pharmaceutical industry for synthesis of different heterocyclic compounds. Chalcone derivatives have variety of biological activities. For the synthesis of chalcone derivatives, Clainsen-Schmidt condensation is widely used method in which strong base abstract proton from alpha position and generates carboanion in presence of alcoholic solvents. Generated carboanion reacts with benzldehyde under condensation and generated chalcones. Reproducibility of this reaction is very poor. In presence study mixture design used to optimize synthetic condition of 2’hydroxy chalcone. Amount of solvent, amount of catalyst, temperature and stirring time was taken as independent variables and % yield taken as dependent variable. After the applying mixture design and ANOVA predicted % yield was 96.55% and experimental value was 95.55%. With the help of mixture design reaction conditions were successfully optimized.

Hydroxy Chalcones and Analogs with Chemopreventive Properties.

The aim of this review is to highlight the chemopreventive properties of hydroxy-substituted natural and synthetic chalcones along with a number of their analogs. These products display various biological activities, and have many applications against various diseases. Antioxidant and anti-inflammatory properties of chalcones bearing hydroxy substituents are underlined. The influence of hydroxy substituents located on ring A, B, or both are systematized according to the exhibited biological properties.

Room temperature imidazolium linked chalcone based ionic LCs: Role of terminal position on mesomorphism

A newly imidazolium linked chalcone ionic LCs (5a-5e, series-1) & (8a-8e, series-2) based on two phenyl rings have been synthesized by the quaternization of 1-methylimidazole and ortho & para-substituted hydroxy chalcone derivatives. The mesogenic behavior of synthesized ionic mesogens was perceived by POM, DSC and XRD measurements. The structure-property relationship of new class of chalcone linked imidazolium ILCs has been studied. All materials exhibited enantiotropical type mesogenic properties. Few selected ionic derivatives showed LC properties at room temperature with higher temperature range. Smectic C and nematic properties were detected in synthesized ionic compounds. Series-2 showed higher thermal stability of smectic and nematic phase as compared to series-1. The X-ray configurations revealed the coexistence of bilayer smectic C pattern over a well-defined temperature range. The molecular structures of target ILCs were identified by using IR and 1H NMR spectroscopy.

Synthesis, Molecular Docking, and ADMET Study of N1-Hydrogen and N1-Benzoyl Pyrazoline as Antibacterial Agents

Abstract Syntheses of N1-hydrogen and N1-benzoyl pyrazoline derivatives and their antibacterial in vitro and in silico assays have been carried out. N1-Hydrogen pyrazoline derivatives were synthesized by cyclization of 2’-hydroxy chalcone, and the subsequent substitution reaction produced N1-benzoyl pyrazoline derivatives. The in vitro antibacterial assay was carried out by disc diffusion method. In silico evaluation was performed via molecular docking against ecKAS III enzyme (ID PDB: 1hnj) and ADMET prediction was carried out using pkCSM tool. The synthesis results showed that N1-hydrogen and N1-benzoyl pyrazoline derivatives were yielded in 50-83%. Antibacterial test results indicated that the presence of N1-benzoyl substituent decreased the antibacterial activity and was only active on Gram-positive bacteria. In comparison, the N1-hydrogen pyrazolines exhibited good antibacterial activity against both Gram-positive and negative bacteria. The ADMET result confirms that compound 2 has the potential to be evolved as a drug in the future. Keywords: Pyrazoline, Antibacterial, Molecular Docking, ADMET

An optimized method for synthesis of 2’hydroxy chalcone

The main aim of present work is to develop optimised method for synthesis of 2’hydroxy chalcone. 2’hydroxy chalcone was synthesized by Claisen–Schmidt condensation between o-hydroxy acetohenone and benzaldehyde. Variety of bases tried as catalyst for synthesis of 2’hydroxy chalcone. Calcium hydroxide and magnesium hydroxide proved ineffective for synthesis. Lithium hydroxide slightly converts reactant to product. Sodium hydroxide shows best catalytical activity compare to other bases. Isopropyl alcohol proved better solvent then other solvents like methanol, ethanol, acetonitrile, dichloromethane and tetrahydrofuran. In optimization step, effect of solvent and base quantity, stirring time and temperature was examined. Temperature shows drastic effect on product yield and purity. At 0˚C best yield was obtained. Amount of base catalyst also shows significant effect on yield. 20ml of 40% NaOH gives best results for 0.05mol reactants. 50ml IPA was needed for the best results for 0.05mol reactant. In approximate 4h, reaction should be completed. Further stirring was not too much effective.

Synthesis, characterization and antioxidant property of nano-scaled metal complexes of triazine based hydroxy chalcone

ABSTRACT In the present investigation, novel triazine-based chalcone ligand (1-(2,4-dihydroxyphenyl)-3-(4-((4-((4-nitrophenyl)amino)-6-phenoxy-1,3,5-triazin-2-yl)oxy)phenyl) prop-2-en-1-one) (DNPP) is synthesized and used in metal complexes synthesis which contains iron, copper, nickel, and zinc. 1H NMR and IR spectrum of DNPP confirms the formation of the product. UV-Visible spectrum shows a peak around 400–500 nm for d-d transition. SEM with EDX shows the metal complexes is in crystalline state with the size in the range of 20–50 nm. TGA analysis shows the synthesized compound is highly stable and the residue content confirms the presence of metal in the molecular structure. Antioxidant were found out to be <50 μg/ml.

Preparation, spectral study and antimicrobial activity of binary Co(II) complexes derived from 2’-hydroxy chalcones

ABSTRACT. The present work comprises preparation, characterization, thermal behavior and growth inhibitory activity of some novel Co(II) complexes derived from substituted (E)-1-(1-hydroxy-4-iodonaphthalen-2-yl)-3-phenylprop-2-en-1-one (L1) and (E)-1-(4-bromo-1-hydroxynaphthalen-2-yl)-3-phenylprop-2-en-1-one (L2-L6). Newly synthesized metal-ligand complexes were structurally confirmed with suitable spectroscopic technique such as FT-IR, EPR, NMR (both 1H and 13C). XRD analysis for complex C1 confirmed the crystal system; tetragonal and space group; P 42/n: 2 with unit cell dimensions a, b = 13.3516 Å, c = 10.8009 Å; α, β, γ = 90o. The IR and EPR study demonstrated that interaction between metal ions and ligand occurs through carbonyl oxygen and hydroxyl oxygen. From the values of magnetic moment (μ) it was observed that synthesized complexes (C1-C6) are paramagnetic with three unpaired electrons contain one electron in t2g orbital and two electrons in eg orbitals. Further all these complexes have been evaluated in-vitro for their antimicrobial activity against the Gram positive bacteria Staphylococcus aureus, Gram negative bacteria Escherichia coli and the yeast Candida albicans. The complex C1 showed the significant antimicrobial activity, whereas the complexes C2, C4, C5 and C6 are moderately active against the tested pathogens. The antimicrobial data revealed that growth inhibitory activities of complexes were enhanced comparatively than its respective ligands. The enhanced antimicrobial activity is attributed to the presence of halogens (Br, Cl, I) and hydroxyl (OH) active substituents associated with the basic nucleus of complexes. Therefore, the present study helps to develop a new class of antimicrobial analogues.&#x0D; &#x0D; KEY WORDS: Metal complexes synthesis, 1,3-Diaryl-2-propene-1-one, Crystal structure, Thermal properties, Antimicrobial activity&#x0D; &#x0D; Bull. Chem. Soc. Ethiop. 2021, 35(3), 513-524.&#x0D; DOI: https://dx.doi.org/10.4314/bcse.v35i3.4

Regioselective One-pot transformation of 2'-hydroxy chalcones to 3,5-diphenylisoxazole via dehydrogenation of dihydroisoxazolines using Copper salt in DMF

A synthesis of series of 3, 5-diaryl isoxazoles has been described. The Cu salt in DMF with EDU base induces oxidative dehydrogenation of 2-(5-phenyl-4,5-dihydroisoxazol-3-yl) phenol results in the formation of 2-(5-phenylisoxazol-3-yl) phenol in excellent yields under mild reaction conditions. The present protocol contains cheap catalyst, easy workup, normal reaction conditions and high selectivity.

An efficient, ultrasound induced ring closure of hydroxy chalcone in 2-ethoxy ethanol as an green reaction medium and study of antimicrobial potential

Abstract An improved sonochemical condensation has been reported between chloro-substituted hydroxyl chalcones and hydrazine hydrate in 2-ethoxy ethanol as an efficient & alternative reaction medium in presence of sodium acetate and acetic acid to afford 2-pyrazolines. The pyrazolines were obtained in good to excellent yields (80–90%), and were characterized by conventional spectral data and evaluated for their antimicrobial potential. It is observed that the work-up is simple and the results obtained indicate that, unlike classical heating, ultrasound irradiation results in higher yields, shorter reaction times (1.5–2.5 h) and milder reaction conditions. The investigation of antimicrobial potential revealed that all the synthesized compounds shows good to moderate growth inhibiting effect against microorganism tested.

An ESIPT coupled AIE fluorescent probe for biothiols detection and imaging based on a chalcone fluorophore

Biothiols are closely related to numerous physiological and pathological processes in living organisms and cells. Fluorescent probes are powerful tools for sensitive detection and imaging of biothiols in biological samples. In this work, we developed a novel turn-on fluorescent probe DNBS-HCA for biothiols detection based on the simple 2′-Hydroxychalcone (HCA) fluorophore, which possesses an excited-state intramolecular proton transfer (ESIPT) coupled aggregation-induced emission (AIE) characteristic. The 2′-hydroxyl group of HCA fluorophore is caged with a biothiols reactive 2,4-dinitrobenzenesulfonyl (DNBS) moiety, which blocks the ESIPT process and quenches the fluorescence. The reaction between probe and biothiols will produce the HCA fluorophore with large Stokes shift and long-wavelength red fluorescence emission. The biothiols in solutions and living cells can be conveniently detected with the probe DNBS-HCA due to its excellent properties such as simple synthetic procedure, remarkable fluorescence enhancement, good sensitivity, high selectivity and low cytotoxicity. Benefiting from the AIE characteristic, the probe is also applied for biothiols detection on indicator papers with RGB color red values, which can be handily obtained by smartphone app.

Production, thermal and dielectrical properties of Ag-doped nano-strontium apatite and nano h-BN filled poly(4-(3-(2,3,4-trimethoxyphenyl) acryloyl) phenyl acrylate) composites

In present study, 4-(3-(2,3,4-trimethoxyphenyl) acryloyl) phenyl acrylate (AC-TMC) monomer was synthesized from the reaction of trimethoxy-substituted hydroxy chalcone and acryloyl chloride in the presence of triethylamine. The polymerization of AC-TMC was carried out by the free radical polymerization method at 60 °C. Monomer and polymer structures were confirmed by FT-IR, 1H-NMR, 13C-NMR spectroscopy techniques. Polymer composites were filled successfully with Ag doped nano-strontium apatite (Sr-Ag) and nano hexagonal boron nitride (h-BN). Characterization of polymer composites was accomplished using FT-IR, XRD and SEM techniques. Thermal analyzes of polymer and polymer composites were performed in nitrogen atmosphere using thermogravimetry (TGA) and differential scanning calorimetry analysis (DSC) techniques. The dielectric properties of composites were investigated by impedance analyzer in a range of 1 kHz-1 MHz frequency at room temperature. The results showed that with the increasing content of h-BN particles, the glass-transition temperature (Tg) of composites was increased obviously. Moreover, the added h-BN fillers increased the thermal stability of polymer significantly. The dielectric properties of polymer composite were enhanced by adding both Sr-Ag and h-BN fillers. The produced polymer composites can find applications in orthopedic, dental implants and medical field as biomaterial.

Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (S)-Butin.

To elucidate the mechanism of anti-ferroptosis and examine structural optimization in natural phenolics, cellular and chemical assays were performed with 2′-hydroxy chalcone butein and dihydroflavone (S)-butin. C11-BODIPY staining and flow cytometric assays suggest that butein more effectively inhibits ferroptosis in erastin-treated bone marrow-derived mesenchymal stem cells than (S)-butin. Butein also exhibited higher antioxidant percentages than (S)-butin in five antioxidant assays: linoleic acid emulsion assay, Fe3+-reducing antioxidant power assay, Cu2+-reducing antioxidant power assay, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-trapping assay, and α,α-diphenyl-β-picrylhydrazyl radical (DPPH•)-trapping assay. Their reaction products with DPPH• were further analyzed using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Butein and (S)-butin produced a butein 5,5-dimer (m/z 542, 271, 253, 225, 135, and 91) and a (S)-butin 5′,5′-dimer (m/z 542, 389, 269, 253, and 151), respectively. Interestingly, butein forms a cross dimer with (S)-butin (m/z 542, 523, 433, 419, 415, 406, and 375). Therefore, we conclude that butein and (S)-butin exert anti-ferroptotic action via an antioxidant pathway (especially the hydrogen atom transfer pathway). Following this pathway, butein and (S)-butin yield both self-dimers and cross dimers. Butein displays superior antioxidant or anti-ferroptosis action to (S)-butin. This can be attributed the decrease in π-π conjugation in butein due to saturation of its α,β-double bond and loss of its 2′-hydroxy group upon biocatalytical isomerization.

Design, synthesis, docking and biological evaluation of chalcones as promising antidiabetic agents

Diabetes mellitus (DM) is a serious chronic metabolic disorder which occurs due to dysfunction of insulin and therapeutic approaches are poor. It is an under estimation that 387 million people currently suffering globally with diabetic and more than 592 million people may be affected by 2030. It makes an urgent necessity to discover novel drugs to control amplified diabetic populations. In this study, amino chalcones (3a-j) were synthesized and hydroxy chalcones (3g-j) were isolated from natural source such as Sophora interrupta, Clerodendrum phlomidis and Andrographis macrobotrys. Structural elucidation was carried out using Mass, 1H and 13C NMR Spectra. In vivo studies were carried out with alloxan induced diabetic rats (100 mg/kg) which reveals compounds 3c, 3a and 3h have significant antidiabetic efficacy with decreased blood glucose levels in the diabetic rats while compared with control rats. Besides, docking studies with aldose reductase, dipeptidyl peptidase, PPAR and glucosidase were monitored which accomplishes that the compounds 3c, 3i, 3a and 3d have eloquent binding affinity (kcal/mol) with aldose reductase, besides the chalcones 3c, 3b, 3d, 3e and 3i were also showed inhibition with DPP-IV, PPAR-α and α-glucosidase. Also, these compounds explicated distinct interactions i.e., π-π, π-cationic, polar, electrostatic and hydrophobic bonds were observed with key residues of binding pockets. Bioavailability is disclosed with Lipinski rule of five and the design pharmacokinetic as well as pharmacodynamic properties are reliable. Therefore, chalcones were implied as antidiabetic leads for in further studies and could be worthwhile for the development of new classes of effective antidiabetic agents.

2'-Hydroxychalcone Induced Cytotoxicity via Oxidative Stress in the Lipid-Loaded Hepg2 Cells.

Licorice is a common herb used in traditional Chinese medicine, and has been widely used clinically. Physiologically, although it is relatively safe, licorice-induced hepatotoxicity in the presence of other diseases needs to be evaluated. The present study was conducted to investigate the toxicological effects of the bioactive components of licorice in HepG2 cells cultured with or without free fatty acid (FFA). The compounds, isoliquiritigenin, licorice chalcone A, bavachalcone, and 2′-hydroxy chalcone (2′-HC) inhibited cell proliferation at certain concentrations in lipid loaded cells with limited effects on the normal cells. The representative compound 2′-HC (at a concentration of ≥ 20µM) increased the oxygen consumption rate, ATP production, mitochondrial membrane potential, generation of total and mitochondrial reactive oxygen species (ROS) production, and expression of inflammatory cytokines (TNF-α, IL-6, and IL-8) and Caspase-9 protein; and reduced the expression of SOD1. In addition, we found exaggerated lipid accumulation in HepG2 cells treated with FFA. Our results suggest that 2′-HC at a concentration of ≥ 20µM might cause damage to the hepatocytes. The toxicity may be related to excess ROS production and inadequate SOD1 expression, leading to apoptosis, inflammation, and cellular dysfunctions.

Aurones and Analogues: Promising Heterocyclic Scaffolds for Development of Antioxidant and Antimicrobial Agents

Synthesis of some new multi-functional analogues of 2′-hydroxy chalcone containing isoxazole and pyrazole functions were synthesized, and their pharmacological activity was tested. Chalcone derivatives were synthesized by the reaction of 2′-hydroxy acetophenone with various substituted benzaldehydes in a basic medium. Aurones were isolated upon treatment with mercuric acetate. Synthesized chalcones and aurones were converted into the corresponding isoxazole and pyrazole derivatives upon their reaction with hydroxylamine hydrochloride or hydrazine hydrate, respectively. Structures of the compounds were confirmed by spectroscopic methods. All synthesized compounds were tested for antioxidant and antibacterial potential. Some of those demonstrated excellent antioxidant activity, and one product was identified as a promising antimicrobial candidate.

Synthesis and Kinetic Investigations for the Isomerization Process of 2–Hydroxy Chalcone Derivatives

The wide biological activities of flavanones are mainly depends on their physical and chemical properties, thus a number of substituted 2-Hydroxy chalcones have been synthesized, and their isomerization to their corresponding flavanones was studied. In order to determine the rate constant, kinetic experiments were performed using HPLC technique in (9:1) (CH3CN:H2O) medium at different temperature (298-318) K. The obtained results were interpreted by four steps mechanism, which considered the existence of phenoxide ion as the key intermediate. This study performed with a pseudo first order ( reaction in which the rate for the studied compounds follow the sequence 5 andgt; 2 andgt; 1 andgt; 4 andgt; 3, the activation energy have the same sequence for these compounds .The effect of substituents on the rate showed that electronic and steric factors play reasonable role on the stability of the product .

Iodine-mediated direct synthesis of 3-iodoflavones

ABSTRACTMolecular iodine has been used for the regioselective, one pot, direct synthesis of 3-iodoflavones from 2′-allyloxy chalcones, 2′-hydroxy chalcones and flavones. Allyl deprotection, cyclization dehydrogenation and α-iodination of 2′-allyloxychalcones has been achieved in a single step to offer 3-iodoflavones.