Chalcone Analogues Research Articles

Application of Chalcone in the Structural Modification of Natural Products: An Overview.

Natural products frequently display a range of biological activities, yet many exhibit only moderate efficacy during initial evaluations. Often, these natural substances necessitate structural alterations to yield promising lead compounds. Chalcones, characterized by their β-unsaturated carbonyl aromatic ketone structure, are prevalent in plant life and serve as fundamental scaffolds for the biosynthetic precursors of flavonoids and isoflavones. Due to their straightforward synthesis and extensive spectrum of biological effects, chalcones have found extensive application in medicinal chemistry. Chalcone analogs have demonstrated significant potential for drug discovery and development, as structural modifications can both amplify pharmacological efficacy and effectively mitigate toxic side effects. This paper endeavors to delve into the applications of chalcones in the structural modification of natural products, providing a theoretical foundation for future endeavors in derivatization and drug development. The full paper is organized into categories based on the biological activities of the derivatives, including anti-dyslipidemic, antibacterial, antimalarial, anti-inflammatory, anticancer, anti-Alzheimer, and α-glucosidase inhibitory activities.

Novel Tricyclo[4.2.1]Nonane and Bicyclo[2.2.1]Heptane Derivatives: Synthesis, in Vitro Biological Activities and in Silico Studies.

The target benzothiazole derivatives (8a-g) were synthesized starting from norbornene. The addition of dichloroketene to norbornene followed by the reduction of chlorine atoms were synthesized tricyclo[4.2.1.02,5]non-7-en-3-one (4). The condensation of benzaldehyde derivatives with compound 4 were obtained chalcone analogs (6a-g). Finally, benzothiazole derivatives (8a-g) were obtained by the reaction of the chalcone analogs with 2-aminobenzothiol in an acidic medium. The antiproliferative activities of compounds 6a-g and 8a-g were determined against C6 (rat brain tumor) and HeLa (human cervical carcinoma) cell lines using a BrdU cell proliferation ELISA assay with 5-fluorouracil (5-FU) as a standard. In both series, when compared with 5-FU (IC50=3.8 μM for C6 and 16.33 μM for HeLa), the most active compounds against C6 cells were 6a and 8g with IC50 values of 14.13 μM and 29.99 μM, respectively. With this, 6a, 6e, 6f, and 8b were the most active compounds against HeLa cells with IC50 values of 0.8, 1.21, 19.33 and 18.13 μM, respectively. Additionally, the SwissADME online web tool was used to predict the physicochemical and ADME properties of the tested compounds. The results showed that all compounds possess promising predicted physiochemical and pharmacokinetic properties and comply with Lipinski's rule of 5, indicating that they are predicted to be orally bioavailable that they possess a predicted bioavailability score of 0.55. Furthermore, in the SwissADME Boiled-Egg chart, all compounds showed high predicted GIT absorption, while compounds 6a-g showed blood-brain barrier (BBB) permeation, and compounds 8a-g did not. Moreover, none of the compounds was (P-gp) substrates. This study investigated the potential interactions between the antiapoptotic proteins Bcl-2, Bcl-xl, Bcl-w, Brag-1, Bfl-1, and Mcl-1 and compounds 6a, 8b, and 8g through molecular docking studies. The findings suggest that these compounds may effectively inhibit antiapoptotic proteins, as evidenced by significant hydrogen bonds and hydrophobic interactions, particularly with Bcl-xl.

Selective detection of cyanide ion using mechno-chemical synthesized fluorophore: 3-(4-(diphenylamino)phenyl)-1-(phenyl)prop‑2-en-1-one

A novel probe has been developed to find the cyanide ion pollutant in our environment. A new chalcone analog (E)-3-(4- (diphenyl amino) phenyl)-1-(phenyl) prop‑2-en-1-one was synthesized by solvents free mechano-chemical method. To detect numerous anions (CN−, F−, Cl−, Br−, NO3−, SO42−, PO43−, OH−, OAc−) in the DMSO medium, the probe's sensing capabilities were tested using UV–Vis absorption and fluorescence spectroscopy methods. The probe exhibited selectivity and sensitivity towards cyanide ions (CN−) in the presence of the various analytes. The interaction energies with the same anions and their sensing behavior through density functional theory (DFT) calculations were reported. The chalcone derivatives' higher electron affinity accelerates, which can also boost the compound's reactivity to cyanide anions following the intramolecular charge transfer (ICT) mechanism.

Interaction of some chalcone derivatives with calcium channels using a theoretical model

For several years, different drugs have been used to treat heart failure, such as digoxin, captopril, spironolactone, milrinone, levosimedam, dobutamine, and others. However, some of these drugs can produce secondary effects such as arrhythmia, cough, hyperkalemia, and others. Analyzing these data, this study aimed to evaluate the interaction of some chalcone derivatives (1-17) with calcium channels using theoretical models. It is important to mention that 7pjx protein, nifedipine, amlodipine, diltiazem, and verapamil were used as theoretical tools in the DockingServer program. The results showed differences in the interaction of chalcone derivatives compared with nifedipine, amlodipine, diltiazem, and verapamil drugs. Other data indicate that the inhibition constant (Ki) for chalcone analog 1 was lower compared with nifedipine, amlodipine, verapamil, and diltiazem. Besides, other results suggest that Ki for compound 11 was lower compared with nifedipine, verapamil, and diltiazem. All these data suggest that chalcone derivatives 1 and 11 could act as calcium channel inhibitors; this phenomenon could be translated into changes in blood pressure through a decrease in calcium intracellular levels. These data suggest that chalcone derivatives 1 and 11 could be good therapeutic alternatives to treat heart failure.

(E)-2-Benzylidenecyclanones: Part XIX. Reaction of (E)-2-(4'-X-Benzylidene)-1-tetralones with Cellular Thiols: Comparison of Thiol Reactivities of Open-Chain Chalcones and Their Six- and Seven-Membered Cyclic Analogs.

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.

A Comprehensive Review of the Docking Studies of Chalcone for the Development of Selective MAO-B Inhibitors.

Monoamine oxidase B is a crucial therapeutic target for neurodegenerative disorders like Alzheimer's and Parkinson's since they assist in disintegrating neurotransmitters such as dopamine in the brain. Pursuing efficacious monoamine oxidase B inhibitors is a hot topic, as contemporary therapeutic interventions have many shortcomings. Currently available FDA-approved monoamine oxidase inhibitors like safinamide, selegiline and rasagiline also have a variety of side effects like depression and insomnia. In the quest for a potent monoamine oxidase B inhibitor, sizeable, diverse chemical entities have been uncovered, including chalcones. Chalcone is a renowned structural framework that has been intensively explored for its monoamine oxidase B inhibitory activity.The structural resemblance of chalcone (1,3-diphenyl-2-propen-1-one) based compounds and 1,4-diphenyl- 2-butene, a recognized MAO-B inhibitor, accounts for their MAO-B inhibitory activity. Therefore, multiple revisions to the chalcone scaffold have been attempted by the researchers to scrutinize the implications of substitutions onthe molecule's potency. In this work, we outline the docking investigation results of various chalcone analogues with monoamine oxidase B available in the literature until now to understand the interaction modes and influence of substituents. Here we focused on the interactions between reported chalcone derivatives and the active site of monoamine oxidase B and the influence of substitutions on those interactions. Detailed images illustrating the interactions and impact of the substituents or structural modifications on these interactions were used to support the docking results.

The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways

In colorectal cancer (CRC), aberrations in KRAS are associated with aggressive tumorigenesis and an overall low survival rate because of chemoresistance and adverse effects. Ergo, complementary, and integrative medicines are being considered for CRC treatment. Among which is the use of natural chalcones that are known to exhibit anti-tumor activities in KRAS mutant CRC subtypes treatment regimens. Consequently, we examine the effect of two novel compounds (DK13 and DK14) having chalcones with nitrogen mustard moiety on CRC cell lines (HCT-116 and LoVo) with KRAS mutation. These compounds were synthesized in our lab and previously reported to exhibit potent activity against breast cancer cells. Our data revealed that DK13 and DK14 treatment suppress cell growth, disturb the progression of cell cycle, and trigger apoptosis in CRC cell lines. Besides, treatment with both compounds impedes cell invasion and colony formation in both cell lines as compared to 5-FU; this is accompanied by up and down regulations of E-cadherin and Vimentin, respectively. At the molecular level, both compounds deregulate the expression and phosphorylation of β-catenin, Akt and mTOR, which are the main likely molecular mechanisms underlying these biological occurrences. Our findings present DK13 and DK14 as novel chemotherapies against CRC, through β-catenin/Akt/mTOR signaling pathways.

CHALCONE ANALOGUES AS POTENTIAL MEDICINES OF PATHOGENETIC THERAPY OF ALZHEIMER'S DISEASE: IN VITRO SCREENING

Introduction. Alzheimer's disease is one of the most common forms of dementia, the pathogenesis of which is based on the accumulation of β–amyloid plaques in brain structures and the development of cholinergic deficiency. The aim of the study was to evaluate the effect of chalcone analogues on the change in acetylcholinesterase activity and the process of β-amyloid aggregation in vitro. Material and methods. The tested compounds were six bis-substituted chalcone analogues, which were dissolved in dimethylsulfoxide during the analysis to obtain double dilutions. The effect of the studied substances on the activity of acetylcholinesterase was evaluated by the modified Ellman method. The change in the aggregation process of β-amyloid particles was determined in reaction with congo red after 3, 6 and 9 days of incubation. Based on the obtained results of the «% inhibition- concentration» relationships, the IC50 index was calculated, which was expressed in mmol/ml. Results. In the course of the study, it was shown that the analyzed chalcone analogues inhibit the aggregation of β-amyloid particles starting from the 6th day of incubation with a maximum on the 9th day. At the same time, the compounds that showed the highest level of activity were trimethoxy-substituted substances under the codes AZBAX4 and AZBAX6, whose IC50 on the 9th day of the study was 21.4±0.928 mmol/ml and 32.4±0.456 mmol/ml, respectively. Also, a high level of anticholinesterase properties was established for these compounds with IC50 of 35.9±0.991mmol/ml and 25.1±0.261 mmol/ml, respectively. The rest of the tested compounds showed a lower level of activity. Conclusion. The study showed that chalcone analogues under the codes AZBAX4 and AZBAX6 inhibit the activity of acetylcholinesterase and the pro-cess of aggregation of β-amyloid in vitro, which makes these compounds promising for further study in order to develop medicines for the pathogenet-ic treatment of Alzheimer's disease.

Evaluation of PPAR gamma agonists: A molecular docking and QSAR study of chalcone analog

In recent years, chalcones have attracted researchers with their unique structure and promising potential across a wide range of scientific disciplines. They are naturally occurring 1,3-diphenyl-2-propen-1-ones. As well as regulating cell proliferation, differentiation, and angiogenesis, PPARs are also involved in cell differentiation. The present study evaluates the molecular activity of 60 chalcone analogs and two marketed drugs as potential PPAR gamma agonists. Molecular docking studies, structural property calculations, and 2D QSAR studies were carried out to screen the best molecule in the library. The compound coded with 2i was found to have the highest binding affinity and selectivity for PPAR gamma. Firm interactions within 5.0 Å were considered for the docking analysis. Ramachandran plot interpretations also helped us to justify the firm binding at the catalytic site. The correlational studies using the QSAR model were carried out, and the coefficient of regression was found to be 0.9247, and the results were plotted. The 2i was found to be the most suitable compound from the library.

Identification of chalcone analogues as anti-inflammatory agents through the regulation of NF-κB and JNK activation.

To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of chalcone analogues were designed and synthesized. In vitro anti-inflammatory activity of these compounds was evaluated by screening their inhibitory effects on NO production in RAW264.7 cell lines. The most promising compounds 3h and 3l were selected for further investigation by assessment of their dose-dependent inhibitory activity against cytokines such as TNF-α, IL-1β, and IL-6 and PGE2 release. The further study also indicated that 3h and 3l could significantly suppress the expression of iNOS and COX-2 through the NF-κB/JNK signaling pathway. Furthermore, compounds 3h and 3l could also remarkably inhibit the mRNA expression of inflammation-related genes. Meanwhile, 3h could also down-regulate ROS production. Docking simulation was conducted to position compounds 3h and 3l into the iNOS binding site to predict the probable binding mode. In conclusion, this series of chalcone analogues with reasonable drug-likeness obtained via in silico rapid prediction can be used as promising lead candidates.

Церебропротекторное действие нового аналога халкона при экспериментальной черепно-мозговой травме. Фокус на митохондриальный биогенез и нейровоспаление

INTRODUCTION: Currently, the treatment of traumatic brain injuries requires a comprehensive approach which includes, among other things, the use of drugs possessing cerebroprotective activity. As a rule, the action of cerebral protectors is concentrated on separate pathophysiological mechanisms of brain damage, for example, the mitochondrial dysfunction. AIM: To study the effect of a new chalcone analogue on changes in the processes of mitochondrial biogenesis and neuroinflammation in rats with experimental traumatic brain injury. MATERIALS AND METHODS: In the work, rats of Wistar line were used in whom a traumatic brain injury was modeled by a single exposure of the parietal region of the skull to a freely falling weight. The studied compound and the comparison drug, choline alfoscerate, were introduced orally within 7 days after injury, at doses of 50 mg/kg and 150 mg/kg, respectively. The behavioral reactions of the animals were evaluated in the ‘open field’ test. The intensity of neuroinflammation was determined by changes in the concentrations of IL-1β, IL-6 and TNF-α in the brain tissue. The markers of mitochondrial biogenesis were changes in the activity of succinate dehydrogenase and cytochrome c oxidase. RESULTS: In the course of the work, it was found that the use of a new chalcone analogue in conditions of experimental traumatic brain injury facilitates an increase in locomotor and exploratory activity in rats, as well as reduces the level of anxiety. With the introduction of the studied compound, a decrease in the intensity of neuroinflammation reactions was observed, as evidenced by a decrease in the content of IL-1β by 58.8% (p < 0.05), IL-6 by 55.0% (p < 0.05) and TNF-α by 50.7% (p < 0.05) compared with untreated animals. The activity of succinate dehydrogenase and cytochrome c oxidase increased by 63.6% (p < 0.05) and 27.6% (p < 0.05), respectively, when using the studied chalcone analogue. To note, the activity of enzymatic markers of mitochondrial biogenesis in rats treated with chalcone analogue was higher than in animals who were introduced choline alfoscerate. CONCLUSIONS: The study showed for prospects of further investigation of a new chalcone analogues as a complex cerebroprotective agent for treatment of sequelae of a traumatic brain injury.

Synthesis and Biological Activity Evaluation of Novel Chalcone Analogues Containing a Methylxanthine Moiety and Their N-Acyl Pyrazoline Derivatives.

On the basis of the structures of natural methylxanthines and chalcone, a series of novel chalcone analogues containing a methylxanthine moiety, Ia-Ig, and their N-acyl pyrazoline derivatives IIa-IIz and IIaa-IIaf were synthesized and identified through melting points, 1H NMR, 13C NMR, and HRMS. The single crystal of compound IId was obtained, which further illustrated the structural characteristics of the methylxanthine-acylpyrazoline compounds. The biological tests showed that some of them displayed favorable insecticidal activities toward Plutella xylostella L. and were superior to the natural methylxanthine compound caffeine while being comparable with the insecticide triflumuron (e.g., compound Ic: LC50 = 16.8508 mg/L, IIf: LC50 = 1.5721 mg/L, against P. xylostella). Of these compounds, Ic, IIf, and IIu could serve as novel insecticidal leading structures for further study. Some of the compounds showed good fungicidal activities (e.g., compound Ig: EC50 = 14.74 μg/mL, against Rhizoctonia cerealis; IIf: EC50 = 7.06 μg/mL, against Physalospora piricola; IIac: EC50 = 5.37 and 8.19 μg/mL, against Phytophthora capsici and Sclerotinia sclerotiorum, respectively); Ic, Ig, IIa, IIf, IIr, IIs, IIv, IIac, and IIaf could be novel fungicidal leading compounds for further exploration. Furthermore, most of the tested compounds exhibited apparent herbicidal activities against Brassica campestris at a concentration of 100 μg/mL; among others, compound IIa was the best one both toward Brassica campestris and Echinochloa crusgalli and deserves further investigation. The structure-activity relationships of these compounds were also summarized and discussed in detail. The contrast experiment results of compounds C-1 and C-2 showed a positive effect on the biological activity enhancement from the combination of the methylxanthine moiety with the N-dichloroacetyl phenylpyrazoline skeleton. In addition, two 3D-QSAR models with predictive capability were constructed based on the insecticidal and fungicidal activities to afford deep insight into the bioactivity profiles of these compounds. This research provides useful guidance and reference for the discovery and development of novel xanthine natural product-based pesticides.

Potential cognitive enhancers: Discovery and development of multi‐targeting aminoalkyl chalcones

AbstractBackgroundInhibition of acetylcholinesterase (AChE) enzyme is considered as the most promising approach to improve the cognitive deficit complex disorders such as Alzheimer’s disease, dementia etc. The AChE also promote the aggregation of amyloid‐β complexes, mitochondrial dysfunction, a buildup of oxidative stress and neuronal cell death. Consequently, the development of compounds having polyfunctional potential could manage the complex neurodegenerative disorders like Alzheimer’s disease.MethodThe chalcone analogues were developed using bioisosteric replacement and SBDD strategies having improved therapeutic potential. The kinetics and interaction pattern with target protein of designed analogues were further evaluated using in silico methods. The leading compounds were synthesized and evaluated against AChE, AGEs formation with additional radical scavenging potential.ResultThe docking results revealed that synthesized chalcones properly fit into the active gorge of the target enzyme and displayed crucial interactions with the peripheral and catalytic sites of and having drug like properties. The in vitro assays of designed compounds against different targets showed IC50 values in nano to micro molar range.ConclusionThe dynamic simulations of the designed compounds will be carried out to evaluate the stability of the target‐ligand complex. Thus, the designed chalcones could be taken further to improve cognition deficit mainly in Alzheimer’s disease.

Design, Synthesis, and Antiproliferative Activity of Quinazolin-4-One/Chalcone Hybrids via the EGFR Inhibition Pathway.

Quinazolinone scaffolds have drawn international attention due to their potent anticancer activity and therapeutic applications. Furthermore, Chalcone and Oxime are special chemical templates with a wide range of biological activities, including anti-cancer activity. As a result, the purpose of this research is to synthesize and develop a new series of 2-thioxo-3-substituted quinazolin-4-one/chalcone analogues and 2-thioxo-3-substituted quinazolin-4-one/oximes analogues in order to obtain a new cytotoxic agent that can target epidermal growth factor (EGFR) and/or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAFV600E) oncogene. All synthesised compounds were tested for anticancer activity against four human cancer cell lines. The new hybrids' potential anti-cancer mechanism was evaluated using EGFR and BRAF enzymatic tests. The most active molecules within the target enzyme's active site were studied using molecular docking. Apoptosis and cell cycle analysis were also investigated. The target compounds 7a-j (series I) are obtained in high yields by alkylation of 2-mercapto-3-ethyl-(3H)- quinazolin-4-one 3a with acylated chalcones 6a-j. Alkylation of compounds 3b-c with N-(4-acetylphenyl)-2- bromoacetamide 8, the corresponding ketones intermediates 9b-c was produced in high yields. Compounds 7a-j, 9b-c, and 10b-c were tested for their antiproliferative activity against four human cancer cell lines using the MTT assay and doxorubicin as a control drug. The EGFR and BRAF assay tests were used to assess the inhibitory potency against EGFR and BRAF. Compounds 7c, 7d, 7f and 10c exhibited high proliferative activity and inhibited EGFR, which could serve as a potential target for antiproliferative activity. The most active hybrid, 7c, primarily caused cell cycle arrest in G0/G1 phase and S phase as well as cell apoptosis. Finally, the most active hybrids were docked well to the EGFR active site. 2-thioxo-3-substituted quinazolin-4-one/chalcone derivatives have significant apoptotic and antiproliferative properties.

Development of chalcone-like derivatives and their biological and mechanistic investigations as novel influenza nuclear export inhibitors

Concerning the emergence of resistance to current anti-influenza drugs, our previous phenotypic-based screening study identified the compound A9 as a promising lead compound. This chalcone analog, containing a 2,6-dimethoxyphenyl moiety, exhibited significant inhibitory activity against oseltamivir-resistant strains (H1N1 pdm09), with an EC50 value of 1.34 μM. However, it also displayed notable cytotoxicity, with a CC50 value of 41.46 μM. Therefore, compound A9 was selected as a prototype structure for further structural optimization in this study. Initially, it was confirmed that the substituting the α,β-unsaturated ketone with pent-1,4-diene-3-one as a linker group significantly reduced the cytotoxicity of the final compounds. Subsequently, the penta-1,4-dien-3-one group was utilized as a privileged fragment for further structural optimization. Following two subsequent rounds of optimizations, we identified compound IIB-2, which contains a 2,6-dimethoxyphenyl- and 1,4-pentadiene-3-one moieties. This compound exhibited inhibitory effects on oseltamivir-resistant strains comparable to its precursor (compound A9), while demonstrating reduced toxicity (CC50 > 100 μM). Furthermore, we investigated its mechanism of action against anti-influenza virus through immunofluorescence, Western blot, and surface plasmon resonance (SPR) experiments. The results revealed that compound IIB-2 can impede virus proliferation by blocking the export of influenza virus nucleoprotein. Thusly, our findings further emphasize influenza nuclear export as a viable target for designing novel chalcone-like derivatives with potential inhibitory properties that could be explored in future lead optimization studies.

Synthesis of novel furan-based chalcone derivatives as anti-tuberculosis agents: in vitro, cytotoxicity assessment and in silico.

Background: The aim of the study is to identify a novel furan-based chalcone derivativeas potent inhibitor against the H37Rv strain. Materials & methods: The in silico pharmacokinetic characteristics, toxicity tests, molecular modeling, chemical synthesis andminimum inhibitory concentration (MIC;IC50)were carried out to evaluate the antitubercular potential of the synthesized furan-based chalcone analogues against H37Rv. Results & conclusion: Among the ten target compounds synthesized, DF02, DF05 andDF07 hadMIC values of 1.6μg/ml equivalent to isoniazid and DF10 showed MIC values of 3.25μg/ml which is equipotent to pyrazinamide. All the other compounds hadoptimal concentrations 6.25-100μg/ml against the H37Rv strain. Compounds DF02 and DF10 werefurther evaluated for cytotoxicity assayperformed using HeLa cell lines.

Exploring the Synthetic Chemistry of Phenyl-3-(5-aryl-2-furyl)- 2-propen-1-ones as Urease Inhibitors: Mechanistic Approach through Urease Inhibition, Molecular Docking and Structure-Activity Relationship.

Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a-s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were condensed with acetophenone via Claisen-Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a-s in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a-s were furnished in good yield (65-90%). Furan chalcone structural motifs 4a-s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a-s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one 4h with an IC50 value of 16.13 ± 2.45 μM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 μM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 μM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.

Molecular Docking Study of Chalcone Analogue Compounds with Hydroxy and Methoxy Subtituents as Bcl-2 Inhibitors

Molecular docking study of 6 chalcone analogues with protein target from the crystallographic structure modeling of Bcl-2 protein with PDB code 2W3L was carried out using computational media using the Molecular Operating Environment (MOE) program. The aim of this study is to determine the potentiality of the 6 chalcone analogue compounds as Bcl-2 inhibitors using molecular docking studies. In this study, venetoclax was used as positive control. Based on docking results, binding free energy was used as information to know which wheather chalcone analogue compounds are active or not as Bcl-2 inhibitors. According to the docking results that have been carried out, it showed that the 6 chalcone analogue compounds have no potential as Bcl-2 inhibitors. Due to the superimposition of the 6 compounds that did not stick to the positive control and most importantly the binding free energy values ​​(S) of the 6 chalcone analogue compounds were higher than the binding free energy values ​​of the positive control (Venetoclax).

The Factor beyond Schmidt's Criteria Impacting the Photo-Induced [2+2] Cycloaddition Reactivity and Photoactuation of Molecular Crystals Based on Cyclic Chalcone Analogues.

Generally, the potential reactive "olefin pairs" in the molecular crystals satisfying Schmidt's criteria could undergo topological [2+2] cycloaddition. In this study, another factor that affects the photodimerization reactivity of chalcone analogues was found. The cyclic chalcone analogues of (E)-2-(2,4-dichlorobenzylidene)-2,3-dihydro-1H-inden-1-one (BIO), (E)-2-(naphthalen-2-ylmethylene)-2,3-dihydro-1H-inden-1-one (NIO), (Z)-2-(2,4-dichlorobenzylidene)benzofuran-3(2H)-one (BFO), and (Z)-2-(2,4-dichlorobenzylidene)benzo[b]thiophen-3(2H)-one (BTO) have been synthesized. While the geometrical parameters for the molecular packing of the above four compounds did not exceed Schmidt's criteria, [2+2] cycloaddition did not occur in the crystals of BIO and BTO. The single crystal structures and Hirshfeld surface analyses revealed that interactions of C=O⋅⋅⋅H (CH2 ) existed between adjacent molecules in the crystal of BIO. Therefore, the carbonyl and methylene groups linked with one carbon atom in carbon-carbon double bond were tightly confined in the lattice, acting as a tweezer to inhibit free movement of the double bond and suppressing [2+2] cycloaddition. In the crystal of BTO, similar interactions of Cl⋅⋅⋅S and C=O⋅⋅⋅H (C6 H4 ) prevented free movement of the double bond. In contrast, the intermolecular interaction of C=O⋅⋅⋅H only exists around the carbonyl group in the crystals of BFO and NIO, leaving the C=C double bonds to move freely and allowing the occurrence of [2+2] cycloaddition. Driven by photodimerization, the needle-like crystals of BFO and NIO displayed evident photo-induced bending behavior. This work demonstrates that the intermolecular interactions around carbon-carbon double bond affect the [2+2] cycloaddition reactivity except for Schmidt's criteria. These findings provide valuable insights into the design of photomechanical molecular crystalline materials.

Novel chalcone analogs derived from 4-(benzyloxy)benzaldehyde

Abstract Eight chalcone analogs were prepared through an aldol condensation starting from 4-(benzyloxy)benzaldehyde and either less common acetophenones or a few selected heteroaryl methyl ketones. The reaction has been performed through the classical approach that employs an alkali as catalyst for five chalcone analogs, while a variant that uses piperidine as basic catalyst was employed for the other three chalcone analogs. The structure of the resulting enones has been established by NMR spectroscopy. Photoinduced dimerization of a selected benzyloxy-substituted chalcone analog under irradiation with UV light for periods of time ranging from 30 minutes to 24 h has also been monitored using NMR spectroscopy. Analysis of the results demonstrated the presence of the E isomer of the chalcone analog along with three regioisomeric cyclobutanes in the irradiated sample.