Natural Chalcone Research Articles

New chalcone derivatives containing morpholine-thiadiazole: Design, synthesis and evaluation of against tobacco mosaic virus

Twenty chalcone derivatives containing morpholine-thiadiazole were designed and synthesized from the natural product chalcone. The bioactivity test results indicate that some compounds exhibit good antiviral activity against tobacco mosaic virus (TMV). In particular, the EC50 values for the curative and protective activity of S14 against TMV were 91.8 and 130.6 μg/mL, which was better than that of the antiviral agent ningnanmycin (NNM, 237.8, 220.6 μg/mL). The results of preliminary mechanism study indicated that S14 had strong binding capacity and affinity to tobacco mosaic virus coat protein (TMV-CP). In the chlorophyll content assay, the chlorophyll content of tobacco leaves increased significantly after the action of S14, so that it can enhance the photosynthetic capacity of plants. In addition, the results of malondialdehyde (MDA) content assay also indicated that S14 could improve the disease resistance of tobacco.

Medicinally Privileged Natural Chalcones: Abundance, Mechanisms of Action, and Clinical Trials.

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.

A Natural Chalcone Cardamonin Inhibited Transformation of Aryl Hydrocarbon Receptor Through Binding to the Receptor Competitively.

Chalcones are widely present in most plants and have various health beneficial functions. This study investigates the suppressive effect of 13 natural and synthetic chalcones on transformation of aryl hydrocarbon receptor (AhR) induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (3-MC) in a cell-free system, Hepa-1c1c7 cells, and liver of ICR mice. In the cell-free system, cardamonin dose-dependently inhibits AhR transformation. Chalcones with substitution on 2' and/or 6' position is important for the suppressive effect, while the substitution on 4' position is negatively for the effect. Moreover, cardamonin and 2'-hydroxychalcone competitively inhibit the binding of [3H]-3-MC to the AhR. In Hepa-1c1c7 cells, cardamonin inhibits AhR transformation and expression of cytochrome P4501A1 (CYP1A1) in a dose-dependent manner through suppressing TCDD-induced phosphorylation of both AhR and AhR nuclear translocator, heterodimerization of them, and nuclear translocation of AhR. In the liver of mice, oral administered cardamonin also inhibits 3-MC-induced AhR translocation and expression of CYP1A1. Among used chalcones, a natural chalcone cardamonin competitively binds to AhR and suppresses its transformation. Thus, cardamonin is an effective food factor for suppression of the dioxin-caused biochemical alterations and toxicities.

Synthesis and biological evaluation of imidazolium conjugated with dimethylcardamonin (DMC) as a novel potential agent against MDA-MB-231 triple-negative breast cancer cells

A new imidazolium ionic liquid (IL) halide conjugated with dimethylcardamonin (DMC, 1), namely [Bbim]Br-DMC (3), was synthesised to improve the biological activity of the natural chalcone. DMC was isolated from seeds of Syzygium nervosum A. Cunn. ex DC. which was an effective anti-breast cancer agent. The compound 1 and 3 showed anticancer activity in MDA-MB-231 cells with IC50 values of 14.54 ± 0.99 μM and 7.40 ± 0.15 μM, respectively. MTT assay showed that compound 3 had cytotoxic effect at least two-fold greater than compound 1 but was low toxic to normal cells of Hs 578Bst. After 48 h, compound 3 at concentration of IC50 value inhibited the proliferation and induced morphological changes of MDA-MB-231 cells in a time-dependent manner. The cell cycle profile also showed that compound 3 exerted anti-proliferation activity with the cell cycle arrest at G0/G1 phase and compound 3 also induced apoptosis and reduced mitochondrial membrane potential in MDA-MB-231 cells in a dose-dependent manner. In gene expression assay, compound 3 up-regulated pro-apoptotic genes such as Bax and p53 and suppressed anti-apoptotic Bcl-2 whereas there was no effect on DNA repair gene such as PARP1. The Bax/Bcl-2 ratio was significantly increased after treated with compound 3. In the molecular docking study, the interactions between compound 3 and B-DNA structure in the minor groove region via hydrogen bonds was reported. In conclusion, [Bbim]Br-DMC or compound 3 is a potential candidate to induce apoptosis and inhibits proliferation via cell cycle arrest and decreases mitochondrial membrane of triple-negative breast cancer MDA-MB-231 cells.

Structure-Activity Relationship of Natural Dihydrochalcones and Chalcones, and Their Respective Oxyalkylated Derivatives as Anti-Saprolegnia Agents.

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.

A Combination of Cardamonin and Doxorubicin Selectively Affect Cell Viability of Melanoma Cells: An In Vitro Study.

Treatment of the most aggressive and deadliest form of skin cancer, the malignant melanoma, still has room for improvement. Its invasive nature and ability to rapidly metastasize and to develop resistance to standard treatment often result in a poor prognosis. While the highly effective standard chemotherapeutic agent doxorubicin (DOX) is widely used in a variety of cancers, systemic side effects still limit therapy. Especially, DOX-induced cardiotoxicity remains a big challenge. In contrast, the natural chalcone cardamonin (CD) has been shown to selectively kill tumor cells. Besides its anti-tumor activity, CD exhibits anti-oxidative, anti-inflammatory and anti-bacterial properties. In this study, we investigated the effect of the combinational treatment of DOX with CD on A375 melanoma cells compared to normal human dermal fibroblasts (NHDF) and rat cardiac myoblasts (H9C2 cells). DOX-induced cytotoxicity was unselective and affected all cell types, especially H9C2 cardiac myoblasts, demonstrating its cardiotoxic effect. In contrast, CD only decreased the cell viability of A375 melanoma cells, without harming normal (healthy) cells. The addition of CD selectively protected human dermal fibroblasts and rat cardiac myoblasts from DOX-induced cytotoxicity. While no apoptosis was induced by the combinational treatment in normal (healthy) cells, an apoptosis-mediated cytotoxicity was demonstrated in A375 melanoma cells. CD exhibited thiol reactivity as it was able to directly interact with N-acetylcysteine (NAC) in a cell-free assay and to induce heme oxygenase-1 (HO-1) in all cell types. And that took place in a reactive oxygen species (ROS)-independent manner. DOX decreased the mitochondrial membrane potential (Δψm) in all cell types, whereas CD selectively decreased mitochondrial respiration, affecting basal respiration, maximal respiration, spare respiratory capacity and ATP production in A375 melanoma cells, but not in healthy cardiac myoblasts. The DOX-induced cytotoxicity seen in melanoma cells was ROS-independent, whereas the cytotoxic effect of CD was associated with CD-induced ROS-formation and/or its thiol reactivity. This study highlights the beneficial properties of the addition of CD to DOX treatment, which might protect patients from DOX-induced cardiotoxicity. Future experiments with other tumor cell lines or a mouse model should substantiate this hypothesis.

Cardamonin inhibits the expression of inflammatory mediators in TNF-α-stimulated human periodontal ligament cells

Objective Periodontis is a chronic inflammatory disease induced by periodontopathogenic bacteria. The excessive immune response caused by persistent bacterial infection leads to alveolar bone resorption and ultimately tooth loss. Cardamonin is a biologically active substance that is found in the Zingiberaceae family, such as Alpinia zerumbet, and is classified as a natural chalcone. There have been no attempts to use cardamonin for the treatment of periodontitis, and no reports have examined the effects of cardamonin on periodontal tissue component cells. The aim of this study was to analyze effects of cardamonin on expression of inflammation mediators produced by TNFα-stimulated human periodontal ligament cells (HPDLCs), including its effects on signal transduction molecules. Methods Cytokine and chemokine levels were measured by ELISA. Protein expression in HPDLCs and activations of signal transduction pathway were determined by Western blotting. Results Our results indicate that cardamonin suppresses C-C motif chemokine ligand (CCL)2, CCL20, C-X-C motif chemokine ligand (CXCL)10, and interleukin (IL)-6 production and intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expression in TNF-α-stimulated HPDLCs. In addition, cardamonin induced the expression of the antioxidant enzyme, Heme Oxygenase (HO)-1, in HPDLCs. Furthermore, cardamonin suppressed TNF-α-stimulated c-Jun N-terminal kinase (JNK), nuclear factor (NF)-κB, and signal transducer and activator of transcription (STAT)3 signaling pathways in HPDLCs. Conclusion We show that cardamonin reduces inflammatory mediator production by inhibiting the activation of several signaling pathways in this manuscript.

Recent Advances in Xanthine Oxidase Inhibitors.

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.

Exploring Butein’s anticancer potential in colorectal cancer: Insights into proliferation inhibition, apoptosis induction, and metastasis suppression via p38 signaling

BackgroundButein, a natural chalcone found in plants, exhibits promising anti-tumor effects across cancers, yet its role in Colorectal cancer (CRC) remain largely unclear. MethodsWe utilized pharmacological, molecular, and in vivo models to assess its impact on CRC cell proliferation, apoptosis, migration, and invasion. Molecular docking and network pharmacology analyses predicted potential target proteins and pathways regulated by Butein. Experimental validations included western blotting, immunohistochemistry, and functional assays. ResultsButein significantly inhibited CRC cell proliferation, induced apoptosis, and disrupted the epithelial-mesenchymal transition (EMT). Its repression of cell migration and invasion capabilities, suggesting potential anti-metastatic properties. The activation of the p38 signaling pathway emerged as a key mechanism mediating Butein’s anti-tumor effects, supported by network pharmacology predictions and experimental evidence. ConclusionThis study highlights the multifaceted anti-cancer potential of Butein in CRC, emphasizing its promising application and the novel role of the p38 pathway.

Synthesis and Biological Applications of Coumarinyl-Chalcones

Abstract: This survey provides information on the synthesis and biological applications of coumarinyl-chalcones. Chalcones are unsaturated ketones involving the reactive ketoethylenic group (CO-CH=CH). Chalcones are naturally abundant in many medical plants, including vegetables, fruits, and foods. Natural and synthetic chalcone compounds exhibit a broad spectrum of biological properties like anticancer, anti-inflammatory, anti-HIV, antioxidant, antimalarial, and antimicrobial. Some conventional, microwave, and grinding techniques have been utilized for the synthesis of chalcones. Noteworthy, the Claisen- Schmidt condensation reaction remains the most popular and effective method for synthesis. It summarizes information about its synthetic methods as building blocks in some reactions like cyclization reactions and medical applications. This review article presents an overview of approaches and biological data for chalcones bearing a coumarin scaffold.

Flavokawain B inhibits NF-κB inflammatory signaling pathway activation in inflammatory bowel disease by targeting TLR2

Inflammatory bowel disease (IBD) is characterized by recurrent inflammatory reactions in the intestinal mucosa, including ulcerative colitis (UC) and Crohn's disease (CD). The expression of Toll-like receptor 2 (TLR2) has been observed to increase during the progression of IBD. Flavokawain B (FKB), a natural chalcone with potent anti-inflammatory activity, exerts its effects through inhibition of the NF-κB pathway. In this study, we aimed to investigate the effects and mechanisms of FKB targeting TLR2 in IBD. C57BL/6 J mice were treated with 2.5% dextran sulfate sodium (DSS) for 7 days, with administration of FKB or TLR2 inhibitor C29 starting on day 2 to establish the model of IBD. In vitro, bone marrow-derived macrophages (BMDMs) were stimulated with the TLR2 agonist Pam3CSK4 to explore the therapeutic effect of FKB and its pharmacological mechanism. Compared with the model group, the FKB-treated group showed significant reductions in colitis-related injuries in the IBD mouse model, including weight gain, increased colon length and reduced inflammation. FKB decreased the formation of TLR2-MyD88 complex by targeting TLR2, leading to suppression of downstream NF-κB signaling pathway. Similar therapeutic effects were observed in the C29-treated group. Additionally, in vitro data suggested that FKB exerted its anti-inflammatory effect by targeting TLR2 and inhibiting Pam3CSK4-induced activation of the NF-κB pathway. The anti-inflammatory effects of FKB were demonstrated through drug affinity responsive target stability assay and cellular thermal shift assay, revealing its binding affinity to TLR2. By inhibiting the activation of the TLR2/NF-κB signaling pathway, FKB effectively prevented DSS-induced IBD and exhibited promising potential as a therapeutic candidate for IBD treatment.

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.

Cardamonin decreases inflammatory mediator expression in IL-1β-stimulated human periodontal ligament cells.

Cardamonin is classified as a natural chalcone, and has been reported to possess various bioactive effects. However, there have been limited attempts to utilize cardamonin in the treatment of periodontitis. This study aimed to investigate whether cardamonin has anti-inflammatory effects on human periodontal ligament cells (HPDLCs), which are a component cell of periodontal tissue. Specifically, the study seeks to determine whether cardamonin affects the expression of inflammatory mediators, such as cytokines and adhesion molecules, induced by interleukin-1β (IL-1β) in HPDLCs, as well as the signaling pathways activated by IL-1β. Cytokine and chemokine levels in supernatants of HPDLCs were measured by ELISA. Western blot analysis was used to measure protein expression and signal transduction pathway activation in HPDLCs. We found that IL-1β-induced CC chemokine ligand (CCL)2, CCL5, CCL20, CXC-chemokine ligand (CXCL)10, and interleukin (IL)-6 production and intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expression in HPDLCs were suppressed by cardamonin treatment. We also found that cardamonin suppressed IL-1β-activated nuclear factor (NF)-κB pathway, and the phosphorylation of signal transducer and activator of transcription (STAT)3. Furthermore, cardamonin treatment enhanced the expression of the antioxidant enzymes, heme oxygenase (HO)-1 and NAD(P)H dehydrogenase [quinone] 1 (NQO1), in HPDLCs. In this study, we found that cardamonin could suppress the production of inflammatory mediators in HPDLCs as well as the activation of several signaling pathways induced by IL-1β treatment.

The Voyage of Natural Chalcone: Isoliquiritigenin

Abstract: This review aims to provide a comprehensive summary of the pharmacological effects of isoliquiritigenin, a natural chalcone. The data was gathered from a variety of research papers published till 2022. The extensive pharmacological features of ISL, including its anti-inflammatory, anti-influenza, anti-tyrosinase, anti-bacterial, anti-sarcoma, anti-oxidative, anti-leiomyoma, anticholera, anti-asthma, anti-diabetic, and anti-cancer activity, neuroprotective, hepatoprotective, and cardioprotective effects, may explain its practical applicability in the treatment and prevention of many illnesses. However, to confirm the target-organ toxicity or side effects, more research is required. The creation and design of new ISL analogues based on previously discovered techniques may benefit from this review.

Antibacterial activity of structurally diverse natural prenylated isobavachalcone derivatives.

Isobavachalcone (IBC) is a natural prenylated flavonoid containing chalcone and prenyl chain moieties with a wide range of biological and pharmacological properties. In this work, we synthesized structurally diversified derivatives (IBC-2 to IBC-10) from the natural prenylated chalcone IBC isolated from Psoralea corylifolia and assessed their antibacterial potency against the Gram-positive and Gram-negative bacterial strains S. aureus ATCC 29213, MRSA ATCC 15187, E. coli ATCC25922 and P. aeruginosa ATCC 27853. IBC and IBC-2 exhibited a minimum inhibition concentration (MIC) of 5.0 μM against S. aureus ATCC 29213, whereas IBC-3 exhibited a broad-spectrum activity against Gram-positive and Gram-negative pathogens. Cytotoxicity assessments on the murine RAW 264.7 macrophage cell line revealed minimal to moderate cytotoxicity for IBC-2 and IBC-3 with a favorable selectivity index (>10). Time- and concentration-dependent studies further supported the bactericidal nature of the compounds, as IBC, IBC-2, and IBC-3 exhibited concentration-dependent killing of S. aureus in a time-dependent manner. Furthermore, combination studies, SEM analysis, and PI staining suggest that IBC-3's mechanism of action targets the bacteria's cytoplasmic membrane or cell wall. The bioactive compounds displayed promising drug-like characteristics and a favorable pharmacokinetic profile (ADME-Tox), indicating a projected high oral bioavailability. Structure-activity relationships (SARs) drawn from this study reveal that a prenyl chain at the A-ring and hydroxy functional groups attached to the aromatic rings of chalcone scaffolds are responsible for this antibacterial potential, which will be helpful in the future discovery and development of antibiotics from natural products to overcome the antibiotic resistance crisis.

Natural chalcone dye-functionalized magnetite nanoparticles: Synthesis, characterizations and performance for the removal of methylene blue and the antibacterial activity

In the present research work, we report the co-precipitation synthesis of size‐controlled of uncoated (Magn) and natural chalcone dye-functionalized superparamagnetic magnetite nanoparticles (Magn_NCD NPs) and the study of their efficiency for the adsorption of methylene blue (MB) as well as their antibacterial activity. The NCD was isolated from Acacia cyanophylla and characterized by using IR, UV–visible and 1H NMR spectroscopies. For the functionalized NPs, the size-control was achieved by varying the pH (pH5 for the sample Magn_NCD5 and pH8 for the sample Magn_NCD8) of the reaction medium. The powders consisted of almost spherical NPs with an average particle size of ∼8, ∼3 and ∼7 nm, for Magn, Magn_NCD5 and Magn_NCD8, respectively. Adsorption study of the MB onto the NPs was conducted by varying the NPs’ nature, the pH, the NPs’ dosage, the MB concentration and the contact time. Regarding the effect of the NPs’ nature on the removal of MB, the smallest NPs (Magn_NCD5) were noticeably more performant. For these NPs, the removal efficiency was found to increase with the increase of pH in the pH range 3–9. Additionally, the adsorption kinetics was studied by the three most applicable kinetic models. The pseudo-second order kinetic model was better suited to the experimental adsorption data. Moreover, the adsorption isotherms were analyzed using the Langmuir, Freundlich, Sips and Redlich–Peterson models. The experimental data were best fitted to the Sips model with an extremely high correlation coefficient. Based on this model, the maximum adsorption capacity was calculated (qm = 125 mg.g−1). The reusability of Magn_NCD5 was also tested. These NPs showed a good reusability; After 5 regeneration-reuse cycles, the decrease in MB removal % was less than 8%. Finally, the antimicrobial activity was carried out against P. aeruginosa (gram-negative) and E. faecalis (gram-positive) bacteria. The Magn_NCD5 showed more zone of inhibition in E. faecalis (19 mm) than P. aeruginosa (14 mm).

Exploring natural chalcones: innovative extraction techniques, bioactivities, and health potential

Chalcones, a class of secondary metabolites within the flavonoid family, are characterized by a distinct C6-C3-C6 structure.

Antibacterial and Cytotoxicity Effect of Flavokawain B Loaded Silver Nanoparticles

: Silver nanoparticles (Ag NPs) are used in sterilizing nanomaterials, medical products, textiles, food storage bags, and personal care products. Ag NPs exhibited significant antibacterial activity due to the sustained release of free Ag. Flavokawain B (FKB) is a natural chalcone extracted from the roots of the kava-kava plant Piper methysticum. In this study, Ag NPs were synthesized by the chemical method using hydrazine hydrate and poly (vinyl alcohol) as reducing and stabilizing agents, respectively. FKB-loaded Ag NPs showed a red shift and were positioned at 421 nm, indicating Ag NPs presence. The FTIR spectrum confirmed the presence of the aromatic compoundand#39;s functional groups (at different absorption bands). The XRD pattern indicated the crystalline nature of the loaded Ag NPs with face-centered cubic (fcc) Ag crystals. SEM image revealed the crystalline nature of FKB-loaded Ag NPs. FESEM image revealed the loading of Ag NPs on the clear and flat surface of FKB, and a spherical shape of Ag NPs with an average size of 60 nm was obtained. The minimum inhibitory concentration (MIC) of AgFKB against Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa was found to be 100 μg/mL. However, 100 μg/mL of FKB discs did not show any inhibition zone in the activity. These findings indicated the improved antibacterial activity of FKB-loaded Ag NPs (Ag-FKB).

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.

Revisiting New Classes of Chalcones from Antidiabetic Perspectives

Elevated blood sugar levels and a plethora of other, more diverse diseases, including changes to protein, carbohydrate, and lipid metabolism, are the only hallmarks of diabetes mellitus. Recent research has shown that mice lacking PTP1B had better glucose tolerance, less diet-induced obesity, and insulin sensitivity in general. In the therapy of serious diabetic problems, natural chalcones have recently been discovered, which have superior selectivity and do not affect pharmacokinetics. This is in response to the present demand for improved PTP-1B inhibitors. No appropriate formulation has been developed for the inhibitors based on natural products chalcones as they have not been tested clinically for toxicological characteristics. The review article has extensively covered various unknown natural chalcone compounds, such as kuwanon J, kuwanon R, kuwanon V, isoliquiritigenin, xanthoangelol, xanthoangelol D, xanthoangelol E, xanthoangelolF, xanthoangelol K, 4-hydroxyderricin, 5,4’-dihydroxy-6,7- furanbavachalcone, licochalcone A, licochalcone B, licochalcone C, licochalcone D, licochalcone E, echinatin, laxichalcone, broussochalcone, macdentichalcone, (2E)1, 1-(5,7-dihydroxy-2,2-dimethyl-2H-benzopyran-8-yl)}3-phenyl-2-propen-1-one, often known as 2E(abyssinone-VI-4-O-methyl ether, 1-(5,7-dihydroxy-2,2,6-trimethyl-2H-benzopyran-8-yl)-3-(4-methoxyphenyl)- 2-propen-1-one) show great promise as a diabetic medication because it can inhibit insulin degradation by targeting the therapeutic target protein tyrosine phosphatase 1B (PTP-1B). These chalcone-based PTP-1B inhibitors derived from natural products are not currently used in clinical trials and have not attracted much interest from contemporary medicine due to a lack of clinical investigation into their toxicological profiles necessary to create an appropriate formulation. These chalcone-based PTP-1B inhibitors may soon unlock new opportunities in diabetotherapeutics.