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After the pandemic COVID-19, global health agencies remind us that tuberculosis is the deadliest infectious disease worldwide. As per WHO reports, approximately ten million people are infected with tuberculosis every year. Only a small portion of global cases receive imperative life-saving medicines. Even in the face of enduring efforts in the discovery of effective management of tuberculosis, the disease remains to affect millions of patients worldwide, with a high rate of morbidity and mortality. Considering the low treatment success, high drug treatment failure, and resistance to existing antituberculosis drugs, there is an urgency for the development of new chemical entities as antituberculosis agents. The development of resistance in tuberculosis (TB) patients to the medications used to treat and prevent the disease presents a significant challenge worldwide. Extensive research confines the molecules to counteract this disease has led to identifying many inhibitory pharmacophores. A wide range of compounds has been screened to find a novel ideal drug candidate for curing tuberculosis. Chalcone and its derivatives are considered precursors of flavonoids and isoflavonoids and display a diverse array of reported pharmacological activities including anti-inflammatory and antituberculosis activities. As this field continues to evolve, these molecules present further opportunities for understanding the mechanism of antituberculosis action and the treatment of MDR. Here, we summarize the impact of chalcone derivatives in tuberculosis treatment. The current statuses of various synthetic chalcone-based approaches for tuberculosis treatment are systematically reviewed here. [ABSTRACT FROM AUTHOR]

Under solvent-free conditions and with the help of ultrasonic irradiation, the synthesis of pyrano[3,2-c]chromen and pyrano[3,2-c]quinolin derivatives was promoted by four different ionic liquids. All reaction was performed at 100 °C and had good to excellent yields. 1-butyl-1-methylpyrrolidin-1-ium acetate (A), 1-butyl-1-methylpiperidin-1-ium acetate (B), N,N,N-triethylbutan-1-aminium acetate (C), and tetrabutylammonium acetate (D) as perfect ionic liquids for this reaction show remarkable catalytic activity. The work was simply developed for the reaction of chalcones with 4-hydroxy-1-methylquinolin-2(1H)-one/4-hydroxycoumarin to perform pure products of pyran heterocycles. [ABSTRACT FROM AUTHOR]

The Michael‐type addition of indoles represents one of the most important C−C bonds forming reactions at their C‐3 position. Herein, we present a mild, versatile and sustainable protocol for the efficient preparation of β‐indolylketones via a Michael addition between indoles and chalcones or α,β‐unsaturated ketones in the presence of substituted arylazo sulfones as photoacid generators (PAGs). [ABSTRACT FROM AUTHOR]

This article traces the development of synthetic routes toward 1-indanones containing a β-quaternary carbon center. The recent advancement in the regio- and chemoselective formal (4+1) carbocyclization of chalcones with internal alkynes via rhodium(III) catalysis for the synthesis of 1-indanones is highlighted. [ABSTRACT FROM AUTHOR]

In the context of designing innovative anticancer agents, the synthesis of a series of chalcones bearing a 3,4,5-trimethoxylated A ring and a variety of B rings, including phenols and original heterocycles such as chromones, was conducted. For this end, Claisen–Schmidt condensation was performed in basic or acidic conditions between the common starting material 3,4,5-trimethoxyacetophenone and appropriate aldehydes; this allowed the recovery of fifteen chalcones in moderate–good yields. The synthesized compounds were screened for their antiproliferative activity against colorectal and prostatic cancer cells, using a colorimetric MTT assay. Among the new chromonyl series, chalcone 13 demonstrates an interesting antiproliferative effect, with IC50 values in the range of 2.6–5.1 µM at 48 h. Then, our study evidenced that indolyl chalcone 10 exhibits excellent activity towards the selected cell lines (with IC50 less than 50 nM). This compound has already been described and has been shown to be a potent anticancer agent against other cancer cell lines. Our investigations highlighted apoptosis induction, through several pro-apoptotic markers, of these two heterocyclic chalcones. Considering phenolic chalcones, compounds 2 and 8 were found to be the most active against cell proliferation, exerting their effect by inducing the depolymerization of cell microtubules. The most promising compounds in this series will be selected for application in a strategy of vectorization by either active or passive targeting. [ABSTRACT FROM AUTHOR]

A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro anticancer screening for the thiazole derivatives 2a–2p exhibited broad-spectrum antitumor activity against various cancer cell lines particularly Ovar-3 and MDA-MB-468 cells with a GI50 range from 1.55 to 2.95 μΜ, respectively. Compound 2e demonstrated significant inhibition of tubulin polymerization, with an IC50 value of 7.78 μM compared to Combretastatin-A4 (CA-4), with an IC50 value of 4.93 μM. Molecular docking studies of compounds 2e, 2g, and 2h into tubulin further supported these findings, revealing that they bind effectively to the colchicine binding site, mirroring key interactions exhibited by CA-4. Computational predictions suggested favorable oral bioavailability and drug-likeness for these compounds, highlighting their potential for further development as chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

X-ray crystallography has been used to characterize the title compound for the first time; 1H NMR, 13C NMR and IR spectroscopic data have also been updated from earlier reports. We also report the melting point of the title compound. [ABSTRACT FROM AUTHOR]

Chalcones, secondary plant metabolites, exhibit various biological properties. The introduction of a chlorine and a glucosyl substituent to the chalcone could enhance its bioactivity and bioavailability. Such compounds can be obtained through a combination of chemical and biotechnological methods. Therefore, 4-chloro-2′-hydroxychalcone and 5′-chloro-2′-hydroxychalcone were obtained by synthesis and then glycosylated in two filamentous fungi strains cultures, i.e., Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5. The main site of the glycosylation of both compounds by I. fumosorosea KCH J2 was C-2′ and C-3 when the second strain was utilized. The pharmacokinetics of these compounds were predicted using chemoinformatics tools. Furthermore, antimicrobial activity tests were performed. Compounds significantly inhibited the growth of the bacteria strains Escherichia coli 10536, Staphylococcus aureus DSM 799, and yeast Candida albicans DSM 1386. Nevertheless, the bacterial strain Pseudomonas aeruginosa DSM 939 exhibited significant resistance to their effects. The growth of lactic acid bacteria strain Lactococcus acidophilus KBiMZ 01 bacteria was moderately inhibited, but strains Lactococcus rhamnosus GG and Streptococcus thermophilus KBM-1 were completely inhibited. In summary, chalcones substituted with a chlorine demonstrated greater efficacy in inhibiting the microbial strains under examination compared to 2′-hydroxychalcone, while aglycones and their glycosides exhibited similar effectiveness. [ABSTRACT FROM AUTHOR]

Chalcones have been utilized for centuries as foods and medicines across various cultures and traditions worldwide. This paper concisely overviews their biosynthesis as specialized metabolites in plants and their significance, potential, efficacy, and possibility as future medicines. This is followed by a more in-depth exploration of naturally occurring chalcones and their corresponding mechanisms of action in human bodies. Based on their mechanisms of action, chalcones exhibit many pharmacological properties, including antioxidant, anti-inflammatory, anticancer, antimalarial, antiviral, and antibacterial properties. Novel naturally occurring chalcones are also recognized as potential antidiabetic drugs, and their effect on the GLUT-4 transporter is investigated. In addition, they are examined for their anti-inflammatory effects, focusing on chalcones used for future pharmaceutical utilization. Chalcones also bind to specific receptors and toxins that prevent bacterial and viral infections. Chalcones exhibit physiological protective effects on the biological degradation of different systems, including demyelinating neurodegenerative diseases and preventing hypertension or hyperlipidemia. Chalcones that are/were in clinical trials have been included as a separate section. By revealing the many biological roles of chalcones and their impact on medicine, this paper underlines the significance of naturally occurring chalcones and their extension to patient care, providing the audience with an index of topic-relevant information. [ABSTRACT FROM AUTHOR]

In this research, we conducted the synthesis of derivatives (2a-c) derived from 4-fluoro-3- methylacetophenone (FMAP) (1) using aldol condensation with substituteddibromobenzaldehydes (a-c). The condensation process occurred in ethanol with the presence of a base, leading to the creation of chalcone derivatives (2a-c). These chalcones serve as crucial intermediates for the production of a diverse array of heterocyclic products. Upon reaction with hydrazine, pyrazol derivatives (3a-c) were obtained, while the use of hydroxylamine hydrochloride resulted in the formation of isoxazole (4a-c). Additionally, the reaction with urea produced oxazine derivatives (5a-c). We characterized all these compounds using spectral techniques, monitoring their reactions through TLC and measuring melting points. Subsequently, we assessed the biological activity of these compounds against two distinct bacterial strains. [ABSTRACT FROM AUTHOR]

The methodologies detail the steps for synthesising a series of chalcones using a protic solvent and 4-fluoro-3-methylacetophenone (FMAA) along with substituted benzaldehydes. In the current investigation, we synthesized chalcone and tested In-silico and In-vitro evaluation. They have tested In-vitro studies for antimicrobial and antifungal activity using the disc-diffusion method. The In-silico analysis of all synthesized derivatives showed a strong binding affinity to the target microorganism proteins, with some compounds displaying the best binding affinity, according to In-vitro research. When compound 1C interacted with the protein Glutaredoxin, it had a-5.43 Kcal/mol affinity. The best binding energies with the proteins UDP-3-O-[3-hydroxymyristoyl] N-acetyl glucosamine deacetylase, DNA gyrase, and dihydrofolate reductase were demonstrated by compound 1D, which has -6.3 Kcal/mol, -5.62 Kcal/mol, and -6.55 Kcal/mol, respectively. [ABSTRACT FROM AUTHOR]

ObjectivesNonalcoholic fatty liver disease is the most common chronic liver disease in children. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been proposed as a treatment for nonalcoholic steatohepatitis (NASH). The aims were to (1) describe pharmacokinetics (PK), safety, and tolerability of oral elafibranor at 2 doses (80 and 120 mg) in children 8-17 years and (2) assess changes in aminotransferases.MethodsChildren with NASH were randomized to open-label elafibranor 80 mg or 120 mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least 1 dose. Standard descriptive statistics and PK analyses were performed.ResultsTen males [mean 15.1 years, standard deviation (SD) 2.2] with NASH were randomized to 80 mg (n = 5) or 120 mg (n = 5). Baseline mean alanine aminotransferase (ALT) was 82 U/L (SD 13) and 87 U/L (SD 20) for 80 mg and 120 mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80 mg and 120 mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC 0-24 , respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120 mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks.ConclusionsOnce daily dosing of elafibranor was well tolerated in children with NASH. There was a 37.4% relative reduction from mean baseline ALT in the 120 mg group. Decreasing ALT may be associated with improvement in liver histology, thus could be considered a surrogate for histology in early phase trials. These results may support further exploration of elafibranor in children with NASH.

Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation of the nicotinic acetylcholine receptor (α7nAChR)-mediated cell-signaling pathways and molecular genes involved in proliferation, angiogenesis, and metastasis. Chalcones (CHs) and their derivatives are intermediate plant metabolites involved in flavonol biosynthesis. Isoliquiritigenin (ILTG), licochalcone A–E (LicoA–E), and echinatin (ECH) are the most common natural CHs isolated from the root of Glycyrrhiza (also known as licorice). In vitro and/or vivo experiments have shown that licorice CHs treatment exhibits a range of pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. Despite advances in NSCLC treatment, the mechanisms of licorice CHs in nicotine-induced NSCLC treatment remain unknown. Therefore, the aim of this paper is to review experimental studies through the PubMed/Medline database that reveal the effects of licorice CHs and their potential mechanisms in nicotine-induced NSCLC treatment.

Molecular dynamics (MD) simulation is an in silico method used in the biomolecular level of research to study how the protein interacts with the target with time. It provides a detailed information of the protein dynamics and ligand structure with the crucial amino acid interactions. Monoamine oxidase B (MAO−B) is a crucial isoenzyme responsible for the catalyses of oxidative deamination of various biogenic amines in the brain and peripheral tissues. The selective inhibitors of MAO−B are considered as the management of symptoms of neurodegenerative disorders like Alzheimer's disease(AD) and Parkinson disease(PD). Recently the structural scaffolds containing chalcones, coumarins and chromones derived candidates shown potent, selective, competitive and reversible type of MAO−B inhibitors. The structural similarities between the above scaffolds can produce almost similar type of interactions in the inhibitor binding cavity of MAO−B. Numerous molecular simulation reports were supported by the above mentioned fact. The current review focus on the last ten year molecular dynamics report of chalcones, coumarins and chromones towards MAO−B inhibition. The review also focuses on the software details used in the MD dynamics simulation and the structural requirement from each class of compound for the recognition of MAO−B inhibitory activity. [ABSTRACT FROM AUTHOR]

Non-enzyme-catalyzed thiol addition onto the α,β-unsaturated carbonyl system is associated with several biological effects. Kinetics and diastereoselectivity of non-enzyme catalyzed nucleophilic addition of reduced glutathione (GSH) and N-acetylcysteine (NAC) to the six-membered cyclic chalcone analogs 2a and 2b were investigated at different pH values (pH 3.2, 7.4 and 8.0). The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended both on the substitution and the pH. The stereochemical outcome of the reactions was evaluated using high-pressure liquid chromatography with UV detection (HPLC-UV). The structures of the formed thiol-conjugates and the retro-Michael products (Z)-2a and (Z)-2b were confirmed by high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Frontier molecular orbitals and the Fukui function calculations were carried out to investigate their effects on the six-membered cyclic analogs. Data were compared with those obtained with the open-chain (1) and the seven-membered (3) analogs. The observed reactivities do not directly relate to the difference in in vitro cancer cell cytotoxicity of the compounds. [ABSTRACT FROM AUTHOR]

Ovarian cancer ranks among the most severe forms of cancer affecting the female reproductive organs, posing a significant clinical challenge primarily due to the development of resistance to conventional therapies. This study investigated the effects of the chalcone derivative 1C on sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines. Our findings revealed that 1C suppressed cell viability, induced cell cycle arrest at the G2/M phase, and triggered apoptosis in both cell lines. These effects are closely associated with generating reactive oxygen species (ROS). Mechanistically, 1C induced DNA damage, modulated the activity of p21, PCNA, and phosphorylation of Rb and Bad proteins, as well as cleaved PARP. Moreover, it modulated Akt, Erk1/2, and NF-κB signaling pathways. Interestingly, we observed differential effects of 1C on Nrf2 levels between sensitive and resistant cells. While 1C increased Nrf2 levels in sensitive cells after 12 h and decreased them after 48 h, the opposite effect was observed in resistant cells. Notably, most of these effects were suppressed by the potent antioxidant N-acetylcysteine (NAC), underscoring the crucial role of ROS in 1C-induced antiproliferative activity. Moreover, we suggest that modulation of Nrf2 levels can, at least partially, contribute to the antiproliferative effect of chalcone 1C. [ABSTRACT FROM AUTHOR]

Saprolegnia sp. is a pathogenic oomycete responsible for severe economic losses in aquaculture. To date, there is no treatment for its control that is effective and does not pose a threat to the environment and human health. In this research, two dihydrochalcones 1 and 2, and three chalcones 3–5, isolated from the resinous plant Adesmia balsamica, as well as their synthesized oxyalkylated derivatives 6–29 already reported and a new synthesized series of oxyalkylchalcones 30–35, were evaluated for their anti-saprolegnia activity and structure–activity relationship as potential control and treatment agents for strains of Saprolegnia parasitica and S. australis. Among the molecules tested, natural 2′,4′-dihydroxychalcone (3) and new oxyalkylchalcone 34 were the most potent antisaprolegnia agents against both strains, even with better results than the commercial control bronopol. On the other hand, the structure–activity relationship study indicates that the contributions of steric and electrostatic fields are important to enhance the activity of the compounds, thus the presence of bulky substituents favors the activity. [ABSTRACT FROM AUTHOR]

The use of halogen bonding interactions as an alternative to acid and metal catalysts for substrate activation has gained popularity in recent years. In this work we demonstrate a halogen bond assisted activation of chalcones under visible light irradiation for the Friedel‐Crafts reaction with indole to yield β‐indolylketones. The simple and scalable protocol uses the readily available CBr4 as halogen bond catalyst. The targets are produced in 31–94% of yield with excellent functional group tolerance. The proposed mechanism of the reaction is supported by UV‐vis, fluorescence, and NMR spectroscopic studies. Further it is demonstrated that the β‐indolylketones can be oxidised to indole substituted α, β‐unsaturated ketones by DDQ or cyclized to thieno[2,3‐b]indoles in the presence of elemental sulfur and base. [ABSTRACT FROM AUTHOR]

The main building blocks for the production of flavonoids and iso-flavonoids are chalcones. Chalcones are α, β-unsaturated carbonyl compounds containing three carbons. The condensation products of aromatic aldehydes with acetophenones in the presence of a catalyst are called chalcones. Numerous techniques and plans have been documented for the synthesis of these substances. Aldol condensation and Claisen–Schmidt condensation continue to hold a prominent position among all. Chalcones and their derivatives have a broad range of pharmacological activities due to presence of reactive α,β-unsaturated carbonyl group. Numerous chalcone-heterocycle hybrids seem to show promise as potential medication candidates based on a review of the literature because of their comparable or better activity than the standards. As a result, the creation and development of novel, highly effective therapeutic medications based on previously established techniques may benefit from this review. [ABSTRACT FROM AUTHOR]

A simple, efficient, and environmentally friendly method was developed for the preparation of chalcones via the Claisen–Schmidt reaction, using an Algerian montmorillonite exchanged by different cations (Ce3+, Co2+, Fe2+ and Fe3+) as a heterogeneous catalyst. The effect of the exchanged cations as well the evaluation of the effects of other parameters on the yield and the kinetics of the reaction were investigated. The obtained results show that our exchanged montmorillonite has superior and satisfactory catalytic properties compared to the homogeneous catalysts, taking into consideration its other advantages, such as being easy to recover and to be regenerated within the reaction medium, being cost-effective, and conforms to the concept of green chemistry. The study also relates to the effects of some parameters on the yield and the kinetics of the reaction, the effects of the catalyst amount, type of solvent, and temperature. [ABSTRACT FROM AUTHOR]

Caneeracone A (1), a new chalcone derivative, together with three known compounds (2–4), was isolated from the seeds of Persea americana Mill. (buccaneer avocado). The structures of these compounds were established by spectroscopic methods including 1D and 2D NMR experiments. Compound 1 exhibited a potent tyrosinase activity with an IC50 of 38.29 μM. [ABSTRACT FROM AUTHOR]

Diabetes mellitus type 2 (T2DM) is a common chronic condition that presents as unsettled hyperglycemia (HG) and results from insulin resistance (IR) and β-cell dysfunction. T2DM is marked by an increased risk of microvascular and macrovascular complications, all of which can be the cause of increasing mortality. Diabetic nephropathy (DNE), neuropathy (DNU), and retinopathy (DR) are the most common complications of diabetic microangiopathy, while diabetic cardiomyopathy (DCM) and peripheral vascular diseases are the major diabetic macroangiopathy complications. Chalcones (CHs) are in the flavonoid family and are commonly found in certain plant species as intermediate metabolites in the biosynthesis of flavonoids and their derivatives. Natural CHs with different substituents exert diverse therapeutic activities, including antidiabetic ones. However, the therapeutic mechanisms of natural CHs through influencing genes and/or signaling pathways in T2DM complications remain unknown. Therefore, this review summarizes the existing results from experimental models which highlight the mechanisms of natural CHs as therapeutic agents for T2DM complications. [ABSTRACT FROM AUTHOR]

The synthesis of novel 5-(2-((1(E/Z),2E)-1,3-disubstitutedallylidene)hydrazinyl)-1,3-dimethyl-4-nitro-1H-pyrazole (4a–k) was attempted via reaction involves a nucleophilic attack which takes place at the carbonyl group of the α,β-unsaturated carbonyls. The transformation proceeds via an effective addition-elimination reaction in the presence of catalytic amount of concentrated H2SO4. The cytotoxicity of synthesized compounds was evaluated against two tumor cell lines, MCF-7 and MDA-MB-231, via MTT assay. The compounds 4a–d showed better toxicity than tamoxifen on MCF-7 cells, ranging from 26.28 to 12.96 µM with 4b having the lowest IC50 among the compounds tested. On the other hand, the compounds have moderate toxicity on MDA-MB-231 with 4c showing the lowest IC50. The docking study suggests that these Schiff bases chalcone scaffolds might facilitate the further development of investigated compounds as anticancer agents. [ABSTRACT FROM AUTHOR]

A multicomponent Kröhnke reaction route toward 2‐trifluoromethyl pyridines from reaction of chalcones with easily available and stable 1‐(3,3,3‐trifluoro‐2‐oxopropyl)pyridin‐1‐ium bromide and ammonium acetate is reported. The reaction is found to be general with a range of substituted chalcones, and the applicability of the methodology in gram scale is demonstrated. Preliminary results suggest that this transformation is initiated by 1,4‐Michael addition, followed by inter‐ and intramolecular nucleophilic addition, and elimination. [ABSTRACT FROM AUTHOR]

Based on the wide range of pharmacological aspects related to organophosphates, a new type of chalcone‐phosphonate containing derivatives were synthesized by the reaction of dialkyl phosphite and substituted chalcones using anhydrous Mg(ClO4)2 at 80 °C under solvent‐free conditions. The resulting compounds were evaluated for anti‐proliferative activity in vitro against a panel of three human cancer cell lines: MCF7, HeLa, and A549 cell lines. Compound 3 l, 3 m, and 3 p exhibited anti‐proliferative activity against MCF7 and HeLa, with IC50 values of 1.12 μM, 1.63 μM, 1.09 μM and 1.29 μM, 1.44 μM, 2.40 μM respectively. The molecular docking study showed that the synthesized derivatives have good binding ability in the active site of the Vaccinia H1‐related (VHR) phosphatase (PDB: 3F81), PI3‐ kinase (PDB: 3R7Q), androgen receptor (PDB: 3V49) and VEGFR2 kinase (PDB: 3VHE). Finally, in silico pharmacokinetic (ADME) and toxicity studies revealed that compounds have the drug‐like feature for the favourable bioavailability. In conclusion, this work confirmed the potency of chalcone‐phosphonates derivatives for the further optimization of potential anti‐ proliferative agents. [ABSTRACT FROM AUTHOR]

We developed a new approach for the synthesis of flavanone from chalcones without electrical energy, such as stirring or heating, by using a cesium fluoride–crown ether complex. This "zero electrical energy reaction" is a new category of reaction that has the potential to replace the general organic reaction. [ABSTRACT FROM AUTHOR]

Ten novel 4-esterchalcones, licochalcone analogues, were strategically synthesized to study the effect of electro-donating or electro-withdrawing substituents in the aryl enone moiety on their pharmacological and photoprotective properties. 4-Esterchalcones had their drug-like character evaluated, which demonstrated positive characteristics for the development of novel drug candidates. In the in vitro antimicrobial evaluation, isovaleryl 4-esterchalcones showed activity against strains of Staphylococcus aureus, Candida albicans and C. tropicalis with minimum inhibitory concentration (MIC) in the range of 2.64-3.32 µmol mL−1, and the isobutyryl 4-esterchalcone 5d (4'-Br) presented antimicrobial activity against all strains tested, with a MIC of 2.74 µmol mL−1. In the UV-Vis study, λmax were observed at 312-327 nm, the UVB range, mainly. The best SPF-UVB results ranged from 18.04 to 21.06, with high εmax values, indicating that 4-esterchalcones have the potential to act as sunscreens. Furthermore, along with the environmental concern, halogenated compounds demonstrated slightly toxic on Artemia salina. [ABSTRACT FROM AUTHOR]

The Pt‐cathode hydrogen evolution reaction (Pt‐HER) of acetone cyanohydrin provides an alternative method for introducing the cyano group onto electrophilic carbons of imines and chalcones. The synthesis of α‐aminonitriles and β‐cyano ketones has been achieved smoothly with a small excess of cyanating agent (2 equivalent), catalytic amount of supporting electrolyte and low electricity consumption (0.02 F/mol). Besides demonstrating a general atom economy, the high Faradaic efficiency, allows for a scale‐up with low‐demanding electrochemical design and short electrolysis times. [ABSTRACT FROM AUTHOR]

A straightforward protocol has been developed to access 3-selenylated pyrazolo[1,5-a]pyrimidines from readily available amino pyrazoles, chalcones, and diaryl/dialkyl diselenides. This I2-catalyzed methodology is highly useful for synthesizing a wide range of functionalized 3-(aryl/alkylselanyl)pyrazolo[1,5-a]pyrimidine derivatives. Mechanistic investigation disclosed that iodine catalysis is very important in both the cyclization process as well as in the C-H selenylation step. Moreover, the developed reaction conditions are also applicable for the cyclization of amino pyrazole with enaminone followed by C-H selenylation in one pot. The use of simple reagents and catalyst, wide substrate scope, mild and metal-free reaction conditions, and practical applicability are the attractive facets of this approach. [ABSTRACT FROM AUTHOR]

Senolytics are drugs that specifically target senescent cells. Flavonoids such as quercetin and fisetin possess selective senolytic activities. This study aims to investigate if chalcones exhibit antisenescence activities. Anti-senescence effect of 11 chalcone derivatives on the replicative senescence human aortic endothelial cells (HAEC) and human fetal lung fibroblasts (IMR90) was evaluated. Compound 2 (4-methoxychalcone) and compound 4 (4-bromo-4'-methoxychalcone) demonstrated increased cytotoxicity in senescent HAEC compared to young HAEC, with significant differences on IC50 values. Their anti-senescence effects on HAEC exceeded fisetin. Higher selectivity of compound 4 toward HAEC over IMR90 could be attributed to 4-methoxy (4-OMe) substitution at ring A (R1). Chalcone derivatives have potentials as senolytics in mitigating replicative senescence, warranting further research and development on chalcones as anti-senescent agent. [ABSTRACT FROM AUTHOR]

Summary: Legume nodulation requires the detection of flavonoids in the rhizosphere by rhizobia to activate their production of Nod factor countersignals. Here we investigated the flavonoids involved in nodulation of Medicago truncatula.We biochemically characterized five flavonoid‐O‐methyltransferases (OMTs) and a lux‐based nod gene reporter was used to investigate the response of Sinorhizobium medicae NodD1 to various flavonoids.We found that chalcone‐OMT 1 (ChOMT1) and ChOMT3, but not OMT2, 4, and 5, were able to produce 4,4′‐dihydroxy‐2′‐methoxychalcone (DHMC). The bioreporter responded most strongly to DHMC, while isoflavones important for nodulation of soybean (Glycine max) showed no activity. Mutant analysis revealed that loss of ChOMT1 strongly reduced DHMC levels. Furthermore, chomt1 and omt2 showed strongly reduced bioreporter luminescence in their rhizospheres. In addition, loss of both ChOMT1 and ChOMT3 reduced nodulation, and this phenotype was strengthened by the further loss of OMT2.We conclude that: the loss of ChOMT1 greatly reduces root DHMC levels; ChOMT1 or OMT2 are important for nod gene activation in the rhizosphere; and ChOMT1/3 and OMT2 promote nodulation. Our findings suggest a degree of exclusivity in the flavonoids used for nodulation in M. truncatula compared to soybean, supporting a role for flavonoids in rhizobial host range. [ABSTRACT FROM AUTHOR]

Chalcones (trans-1,3-diphenyl-2-propen-1-ones) form simple chemical structures that act as precursors for the biogenesis of flavonoids. These are distributed in plants and have two aromatic or heteroaromatic rings connected by a three-carbon α, β-unsaturated carbonyl group. Considering the importance of chalcones as monoamine oxidase and acetylcholinesterase inhibitors, the study was designed as a comprehensive and systematic analysis to evaluate the pharmacological activities leading to the formation of drug molecules against Alzheimer's disease (AD). Based on our previous research, 11 indolyl chalcones (IC1–IC11) were synthesised and investigated for MAO-B inhibitory activity. The inhibitory potential was evaluated based on binding and reversibility studies using purified enzymes. The active and most promising molecule, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9), also found predominant acetylcholinesterase inhibition and hence it was found dual acting in vitro. Based on this, the molecule IC9 was further subjected to cell line studies to further explore its role as a neuroprotective agent against neuronal degeneration, one of the main contributing parameters related to AD. [ABSTRACT FROM AUTHOR]

A rise in infections caused by methicillin- and vancomycin-resistant Staphylococcus aureus is an increasing global health concern that causes boosting illness and death. The growing problem of drug resistance has emphasized the need to discover and develop new antibacterial agents that work through different mechanisms. To address this issue and create prospective antibacterial drugs, numerous chalcone derivatives of thiazolidine-2,4-dione have been designed, synthesized, and evaluated against three bacterial strains and one fungal strain. Compounds 7a, 7h, and 7k were found to selectively inhibit S. aureus at a concentration of 25 μg/mL but were inactive toward gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Two series of new ferrocenyl pyrazolines have been synthesized by the reaction of ferrocenyl chalcones and their analogues with hydrazine hydrate in the presence of corresponding carboxylic acid. Single‐crystal X‐ray crystallographic data were used for detailed analysis of the interesting versatility of four compounds in the formation of intermolecular interactions. The analysis revealed an excellent structural flexibility of the present ferrocenyl pyrazoline molecules for the non‐covalent interactions, with a particular contribution of the ferrocene units. In addition, for comparison with crystallographic findings, we investigated the protective effect of all compounds on DNA against hydroxyl and peroxyl radicals induced by Fe2+, H2O2, and 2,2′‐azobis(2‐amidinopropane) dihydrochloride (AAPH). The results indicated that all compounds showed rather similar DNA protective activity, which was comparable with quercetin as a well‐known protective compound. This similarity in antigenotoxic action could be explained by the established excellent structural flexibility of ferrocenyl pyrazolines for the formation of different intermolecular interactions as important structural property for molecular recognition. [ABSTRACT FROM AUTHOR]

In this work, we have disclosed a facile metal-free synthesis of pharmaceutically fascinating and biologically important benzothiazepines in the presence of a few drops of ethanol. The present methodology converts chalcones and ortho -amino thiophenol into 2,3-dihydro-1,5-benzothiazepines under ambient conditions using liquid-assisted grinding, resulting in rapid synthesis in a very short period. This process is eco-friendly, operationally simple and gives good to excellent yields of products with easy isolation. This approach offers a facile synthesis of 2,3-dihydro-1,5-benzothiazepines from three readily available starting materials. An electrochemical study of the benzothiazepine derivatives was undertaken using cyclic voltammetry and electrochemical impedance spectroscopy techniques. This article introduces a metal-free, liquid-assisted grinding method for synthesising 2,3-dihydro-1,5-benzothiazepine systems. This protocol offers the benefits of non-hazardous reaction conditions, quick reaction times, tolerance to various functional groups and easy product isolation. It utilises the cost-effective tools of a mortar and pestle. Electrochemical techniques are also employed to determine the electrochemical properties and diffusion coefficients of 2,3-dihydro-1,5-benzothiazepine derivatives that can be helpful in their application in the pharmaceutical industry. This innovative approach shows promise for synthesising therapeutic derivatives and their applications. (Image credit: Manjit Singh.) [ABSTRACT FROM AUTHOR]

Salmonellosis has a high power of dissemination and dispersion of strains resistant to conventional antimicrobials, which constitutes a public health problem. Nanoemulsions can enhance the efficacy of antimicrobials compared to conventional drug administration, with reduced side effects and prolonged release. The aim of this study is to produce nanoemulsions by high-energy method using alginate and gum arabic matrices to evaluate the effect of three types of chalcone on the inhibition of S. minnesota and to propose an alternative candidate to overcome antibiotic resistance in pathogenic bacteria. Nanoemulsions with nanosized spherical particles obtained with gum arabic are more stable over time than those with alginate by the lower sedimentation values and the smaller size of the droplets. The antibacterial inhibition test against S. minnesota revealed that the chalcone 1,5-di(thiophen-2-yl)penta-1,4-dien-3-one (TIOF) and 1,5-bis(4-ethoxyphenyl)penta-1,4-dien-3-one (ETOX) and their nanoemulsions presented an equivalent effect compared to the positive control (sulfamethoxazole-trimethoprim). On the other hand, although the chalcone 1,9-diphenylnone-1,3,6,8-tetraen-5-one (CNM) presented low inhibitory capacity, they presented an increasing in the inhibitory activity of 164%, when they were in the nanoemulsion form in comparison with the free form, and equivalent activity to the positive control. Nanoemulsions of gum arabic with 1,9-diphenylnone-1,3,6,8-tetraen-5-one (CNM) also presented lower cytotoxic effects, being a promising inhibitor against S. minnesota. [ABSTRACT FROM AUTHOR]

The biodeterioration of archaeological mummies is a severe issue, where fungi are the most significant agents deteriorating them. The inhibitory effect of [1,2,4]triazolo[3,4-a]isoquinoline chalcone derivatives on the growth of thirteen deteriorated fungal species (Aspergillus flavus, A. niger, A. terreus, Athelia bombacina, Aureobasidium iranianum, Byssochlamys spectabilis, Cladosporium cladosporioides, C. ramotenellum, Penicillium crustosum, P. polonicum, Talaromyces atroroseus, T. minioluteus, and T. purpureogenus), which isolated and identified from ancient Egyptian mummy cartonnage located in El-Lahun regions, Fayoum government, Egypt were investigated. Antifungal activity and minimal inhibitory concentration (MIC) of the tested four chalcone derivatives with different concentrations (1, 2, 3, 4, 5, 6 mg/ml) were measured. The most efficient chalcone derivatives are chalcone derivative number 4 which causes the maximum significant inhibition in the growth of the thirteen isolated fungal species with MIC ranging from 1 to 3 mg/ml followed by chalcone derivatives number 6 with MIC ranging from 2 to 5 mg/ml. The use of chalcone derivative number 4 for the preservation of cultural assets should be considered for future applications. [ABSTRACT FROM AUTHOR]

Methoxychalcones containing the NMe2, 3,4-(OMe)2, 3,4,5-(OMe)3, and isobornyl substituents in the B ring were synthesized from 1,3-dihydroxy-4-(1,7,7-trimethylbicyclo-[2.2.1]hept-exo-2-yl)benzene and 1,4-dihydroxy-3-(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl)benzene. Oxidative cyclization of the new isobornylchalcones afforded flavones bearing the 1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl moiety. The erythrotoxicity, membrane-protective, and antioxidant activity of the synthesized compounds were evaluated in in vitro models including the model of oxidative hemolysis of mammalian erythrocytes initiated by H2O2 or 2,2′-azobis-(2-amidinopropane) dihydrochloride. All the chalcones studied and most flavones possessed good hemocompatibility and high antioxidant activity. The promise of further research into the synthesis of effective pharmacological substances based on the title compounds was demonstrated. [ABSTRACT FROM AUTHOR]

Chalcone and its derivatives have attracted great attention because of a wide range of biological activities such as, antimicrobial, anticancer, antioxidant, anti-anthelmintic, anti-amoebicidal, antiulcer, antiviral, insecticidal and immunosuppressive. The presence of functional groups and conjugation within the structure make it a good candidate for these applications. This review highlighted the synthesis of chalcone derivatives which were described by researchers and studied their biological activity. [ABSTRACT FROM AUTHOR]

A series of messagenin–based chalcones has been synthesized by Claisen‐Schmidt condensation and screened for in vitro α‐glucosidase inhibitory activity. The heterocyclization of 30‐(3‐pyridinylidene)‐messagenin led to syn/anti N‐acetyl‐pyrazoles in a ratio of 2 : 1 that were isolated by HPLC. Messagenin chalcones act as α‐glucosidase inhibitors with IC50 range from 0.055 to 80.70 μM. The lead nanomolar level α‐glucosidase inhibitor 30‐(4‐hydroxymethyl‐benzylidene)‐messagenin 10 was studied for antihyperglycemic activity on streptozotocin–induced diabetic animal models using in vivo mechanism–based assays. In a rat model of STZ‐induced T1DM, compound 10 (20 mg/kg, orally) exhibited antihyperlipidemic activity, reducing AIP (p>0.05) and CRI (p<0.05) compared to control. Compound 10 improved diabetic nephropathy, locomotor activity in rats, and reduced diabetes–related mortality. [ABSTRACT FROM AUTHOR]

Kinetoplastids are a group of flagellated protozoans including medically important parasites of the genus Trypanosoma and Leishmania. The corresponding diseases have afflicted humans for centuries. In an effort to combat kinetoplastid infections, a set of 21 chalcones was synthesized and evaluated for their in vitro anti-protozoal efficacy against Trypanosoma brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania infantum. To ensure safety, these compounds underwent a selectivity evaluation by assessing toxicity against a human lung fibroblast cell line. Compound K4 exhibited remarkable and selective trypanocidal activity against T. b. brucei with IC50 value of 0.31 ± 0.27 µM and T. b. rhodesiense with IC50 value of 0.96 ± 0.86 µM. Compound K9 also showed significant trypanocidal activity against T. b. brucei (IC50: 0.45 ± 0.14 µM) and T. b. rhodesiense (IC50: 0.93 ± 0.51 µM). In both compounds, electron withdrawing groups are appended to the styrenyl moiety. [ABSTRACT FROM AUTHOR]

Heterocyclic compound such as quinazoline derivatives shows wide range of medicinal application in the area such as anticonvulsant, antitumor, antifungal, antimalaria, anti-hyperlipidemic and anti-inflammatory etc. activity because of these it shows great interest to study. In the presence study, we have synthesized triazole based quinazolinones by condensation reaction between α-methyl ketone and aromatic aldehydes under ethanol as the solvent to produced chalcones derivatives. This chalcone derivative have α,β-unsaturated part which is enhanced the reactivity of compound. Chalcone further reacted with 2-aminotriazole under alkali media in the presence of ethanol as the solvent to produced quinazolinone. This prepared compound has further possibility to modified at N atom upon reaction with halogen containing compound. Prepared quinazolinone were further treated with cyanuric chloride to increase heterocyclic part in the compound. Characterization of all synthesized product were done using spectroscopic techniques. All prepared compounds were screen for their biological evaluation against gram+ve and gram-ve bacteria. [ABSTRACT FROM AUTHOR]

This review article is a comprehensive and current overview on chalcones, covering their sources, identification methods, and properties with a particular focus on their applications in the agricultural sector. The widespread use of synthetic pesticides has not only led to increased resistance among weeds and pests, resulting in economic losses, but it has also raised significant health concerns due to the overuse of these chemicals. In line with the European Green Deal 2030 and its Farm to Fork strategy, there is a targeted 50% reduction in the use of chemical pesticides by 2030, emphasizing a shift towards natural alternatives that are more environmentally sustainable and help in the restoration of natural resources. Chalcones and their derivatives, with their herbicidal, fungicidal, bactericidal, and antiviral properties, appear to be ideal candidates. These naturally occurring compounds have been recognized for their beneficial health effects for many years and have applications across multiple areas. This review not only complements the previous literature on the agricultural use of chalcones but also provides updates and introduces methods of detection such as chromatography and MALDI technique. [ABSTRACT FROM AUTHOR]

A series of 16 novel prenylated chalcones (5A-5P) was synthesized by microwave-assisted green synthesis using 5-prenyloxy-2-hydroxyacetophenone and different benzaldehydes. Comparisons were also performed between the microwave and conventional methods in terms of the reaction times and yields of all compounds, where the reaction times in the microwave and conventional methods were 1-4 min and 12-48 h, respectively. The synthesized compounds were characterized using different spectroscopic techniques, including IR, 1H-NMR, 13C-NMR, and LC-HRMS. The antifungal activities of all compounds were evaluated against Sclerotium rolfsii and Fusarium oxysporum under in vitro conditions and were additionally supported by structure-activity relationship (SAR) and molecular docking studies. Out of the 16 compounds screened, 2'-hydroxy-4-benzyloxy-5'-O-prenylchalcone (5P) showed the highest activity against both S. rolfsii and F. oxysporum, with ED50 of 25.02 and 31.87 mg/L, respectively. The molecular docking studies of the prenylated chalcones within the active sites of the EF1a and RPB2 gene sequences and FoCut5a sequence as the respective receptors for S. rolfsii and F. oxysporum revealed the importance of the compounds, where the binding energies of the docked molecules ranged from -38.3538 to -26.6837 kcal/mol for S. rolfsii and -43.400 to -23.839 kcal/mol for F. oxysporum. Additional docking parameters showed that these compounds formed stable complexes with the protein molecules. [ABSTRACT FROM AUTHOR]

The growing interest in synthesizing electrochemically active organic ligands stems from extensive reports highlighting the applications of redox‐active organic molecules. These molecules play a crucial role in capturing and converting CO2 into valuable organic compounds, including carbonates used as solvents in lithium batteries. In this study, we present an electrochemical investigation of two chalcone derivatives, referred to as (1) and (2). We explored the influence of different solvent systems, specifically acetonitrile and dimethyl sulfoxide, on the reduction potential of these chalcones. The reported chalcone derivatives were characterized using various analytical techniques, including UV/Visible spectroscopy, Fourier Transform Infrared spectroscopy, Proton and Carbon‐13 nuclear magnetic resonance, as well as mass spectrometry. The characterization of the reported chalcones, exhibiting properties of both β‐diketones and 2‐hydroxyphenones, is underscored by a density functional theory (DFT) study of chalcones (1) and (2). This research establishes a correlation between the energies calculated through DFT and the experimental reduction potentials of chalcones (1) and (2), in comparing them with a series of β‐diketones and 2‐hydroxyphenones. [ABSTRACT FROM AUTHOR]

This paper presents four one‐component Type II visible‐light‐absorbing chalcones (CY10‐13) that containing various fused aromatic rings as its π‐conjugated moiety, that is a 2‐naphthalene moiety for CY10, 1‐naphthalene for CY11, benzofuran for CY12, and benzothiophene for CY13. The absorption region changes significantly when introducing various fused aromatic rings. However, they all exhibit good absorption properties ranging from 300 to 450 nm that can be well‐matched under ultraviolet (UV), 365 and 405 nm light irradiations. Furthermore, the structure–reactivity relationship is also studied through thermal, photochemical, electrochemical, and computation properties. Finally, all the chalcones demonstrate photoinitiating ability without additive additional hydrogen donor in their systems. Both of the CY11 and CY12 based photoinitiating formulations initiate sufficiently upon UV and light‐emitting diode (LED)@405 nm light exposures. Furthermore, triphenylamine‐substituted chalcone analogous (CY8) is added for comparison. Although CY10‐13 compounds have lower light harvesting regions than CY8, some of those new chalcones exhibit better photoreactivity. Thus, a chalcone containing fuses aromatic ring featuring straightforward synthesis as well as versatile absorption region and photoinitiating performance, has great potential in photopolymerization applications. [ABSTRACT FROM AUTHOR]

A new series of compounds, namely 2-{[4'-(3"-aryl)-2"-propene-1"-one-phenyl]amino}benzoic acids (3a-3j) and 2-{[4'-(5"-aryl)isoxazol-3"-yl]phenyl amino} benzoic acids (4a-4j), were synthesized. The structures of these compounds were confirmed by 1H NMR, IR, Mass spectral analysis. The compounds (3a-3j) and (4a-4j) have been evaluated their antimicrobial activity. [ABSTRACT FROM AUTHOR]

Introduction: Chalcones, are a group of organic compounds containing two aromatic rings bridged by a three-carbon -a, ?; unsaturated carbonyl system. This attracted much attention because of their versatility in pharmacological profiles. Aims & Objectives: To investigate the therapeutic efficacy of a particular chalcone derivative, namely (E)-1-(4- bromophenyl)-3-(4-chlorophenyl) prop-2-ene-1-one. Place and Duration of Study: It was conducted in the Pharmacology Laboratory of the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, and the University of Malakand for about one year. Material & Method: This was a lab-based experimental study. The therapeutic efficacy of a chalcone derivative, (E)-1- (4-bromophenyl)-3-(4-chlorophenyl) prop-2-ene-1-one was assessed through an experiment on pain and inflammation in mice. Claisen-Schmidt condensation reaction and spectroscopic tools were used. Results: Pharmacological data proved a significant decrease in pain and inflammation as compared to Diclofenac Sodium. Reduction of 75.20% in acetic acid-induced writhing as compared to 84.4% with Diclofenac. After 3 hours, there was 67.08% reduction in edema. Conclusion: This study provides evidence that chalcone derivatives in moderation may be effective and safer than present-day drugs that address pain and inflammation. This result may need to be further clinically related to potentially translate them in different patient populations in terms of efficacy and safety.

X-ray crystallography has been used to characterize the title compound for the first time; 1H NMR, 13C NMR and IR spectroscopic data have also been updated from earlier reports. We also report the melting point of the title compound.