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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120272, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34428636

RESUMO

Hydrazine, as a toxic substance, seriously endangers human health and the environment. Based on the excellent luminescent properties and low biological toxicity of pyrene derivatives, combing with chalcone derivatives easily attacked by nucleophilic group, a pyrene derivative PCA decorated by acryloyl terminal group as fluorescent probe for hydrazine was developed. The compound shows fluorescent peak red shift and intensity enhancement with increasing solvent polarity from hexane (459 nm) to methanol (561 nm). Based on strong fluorescence emission in methanol, methanol-HEPES mixed solution was used as the solvent in the spectral recognition experiments. The probe exhibits fluorescent change from yellow fluorescence (576 nm) to blue fluorescence (393 nm) with 800-fold ratiometric fluorescence enhancement (I393nm/I576nm) after the reaction with hydrazine. The probe can recognize hydrazine in fast response rate with kinetic constant calculated being 2.7 × 10-3 s-1 and 15 min as response time. The probe also can monitor hydrazine in real water samples and various soils.


Assuntos
Chalcona , Chalconas , Corantes Fluorescentes , Humanos , Hidrazinas , Pirenos , Espectrometria de Fluorescência
2.
Int J Mol Sci ; 22(19)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34639190

RESUMO

Calcium signaling plays a vital role in the regulation of various cellular processes, including activation, proliferation, and differentiation of T-lymphocytes, which is mediated by ORAI1 and potassium (K+) channels. These channels have also been identified as highly attractive therapeutic targets for immune-related diseases. Licochalcone A is a licorice-derived chalconoid known for its multifaceted beneficial effects in pharmacological treatments, including its anti-inflammatory, anti-asthmatic, antioxidant, antimicrobial, and antitumorigenic properties. However, its anti-inflammatory effects involving ion channels in lymphocytes remain unclear. Thus, the present study aimed to investigate whether licochalcone A inhibits ORAI1 and K+ channels in T-lymphocytes. Our results indicated that licochalcone A suppressed all three channels (ORAI1, Kv1.3, and KCa3.1) in a concentration-dependent matter, with IC50 values of 2.97 ± 1.217 µM, 0.83 ± 1.222 µM, and 11.21 ± 1.07 µM, respectively. Of note, licochalcone A exerted its suppressive effects on the IL-2 secretion and proliferation in CD3 and CD28 antibody-induced T-cells. These results indicate that the use of licochalcone A may provide an effective treatment strategy for inflammation-related immune diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Chalconas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/antagonistas & inibidores , Canal de Potássio Kv1.3/antagonistas & inibidores , Proteína ORAI1/antagonistas & inibidores , Linfócitos T/efeitos dos fármacos , Cálcio/metabolismo , Sinalização do Cálcio , Células HEK293 , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Células Jurkat , Canal de Potássio Kv1.3/genética , Canal de Potássio Kv1.3/metabolismo , Proteína ORAI1/genética , Proteína ORAI1/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
3.
Nutrients ; 13(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34684383

RESUMO

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in Vmax and an increase in Km, whereas suppression by cardamonin was associated with a reduction in Vmax and no change in Km. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.


Assuntos
Glicemia/metabolismo , Chalconas/farmacologia , Flavonas/farmacologia , Intestinos/fisiologia , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Administração Oral , Aminoácidos/metabolismo , Animais , Células CHO , Células CACO-2 , Chalconas/química , Cricetulus , Flavonas/química , Frutose/metabolismo , Humanos , Cinética , Camundongos Endogâmicos ICR , Compostos Fitoquímicos/farmacologia , Sarcosina/metabolismo , Sódio/metabolismo , Transportador 1 de Glucose-Sódio/metabolismo
4.
Phytomedicine ; 93: 153785, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34638032

RESUMO

BACKGROUND: Acute lung injury (ALI) is a systemic inflammatory process, which has no pharmacological therapy in clinic. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-inflammatory efficacy in several disease models, which could be the potential candidates for the treatment of ALI. HYPOTHESIS/PURPOSE: Anti-inflammatory screening from natural product bank may provide new anti-inflammatory compounds for therapeutic target discovery and ALI treatment. METHODS: 165 natural compounds were screened for their anti-inflammatory activity in LPS-stimulated macrophages. PCR array, SPR and ELISA were used to determine the potential target of the most active compound, Cardamonin (CAR). The pharmacological effect of CAR was further evaluated in both LPS-stimulated macrophages and ALI mice model. RESULTS: Out of the screened 165 compounds, CAR significantly inhibited LPS-induced inflammatory cytokine secretion in macrophages. We further showed that CAR significantly inhibited NF-κB and JNK signaling activation, and thereby inflammatory cytokine production via directly interacting with MD2 in vitro. In vivo, our data show that CAR treatment inhibited LPS-induced lung damage, systemic inflammatory cytokine production, and reduced macrophage infiltration in the lungs, accompanied with reduced TLR4/MD2 complex in lung tissues, Treatment with CAR also dose-dependently increased survival in the septic mice induced by DH5α bacterial infection. CONCLUSION: We demonstrate that a natural product, CAR, attenuates LPS-induced lung injury and sepsis by inhibiting inflammation via interacting with MD2, leading to the inactivation of the TLR4/MD2-MyD88-MAPK/NF-κB pathway.


Assuntos
Lesão Pulmonar Aguda , Chalconas , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Chalconas/farmacologia , Citocinas/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Antígeno 96 de Linfócito , Camundongos , NF-kappa B/metabolismo
5.
Eur J Pharm Sci ; 167: 106029, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34601069

RESUMO

The co-penetration of micellar vehicles and the encapsulated drugs into the skin layers, as well as the mechanisms underlying the penetration enhancement have not been clearly elucidated. We developed licochalcone A (LA)-loaded glycyrrhiza acid (GA) (GA+LA) micelles for topical delivery of LA into the epidermis. The in vitro co-penetration, penetration pathways, mechanism of interaction between skin and the micelles, and the in vitro and in vivo whitening effect of GA+LA micelles were evaluated. Co-penetration and penetration pathways were visualized on the abdominal skin of rats model with confocal laser scanning microscopy (CLSM) using a nile blue A-labeled GA (GA-NB). We found that GA significantly increased the transport of LA into the skin predominantly via the hair follicles and GA mainly accumulated in the SC and epidermis, while LA was localized in the epidermis and dermis. Moreover, 73.4% of the LA deposited into the epidermis within 12 h and approximately 9.32% of the LA permeated across the SC in the form of entire micelles within 24 h. GA-NB+LA micelles disaggregated and accumulated in the specific skin layers, and the LA released from the carrier penetrated into deeper layers. Moreover, the GA+LA micelles promoted drug penetration via intracellular or intercellular routes by loosening the skin surface and enhancing fluidization through lipid distortion and keratin denaturation. Furthermore, GA+LA micelles exhibited synergistic whitening effect on B16 cells and UVB-exposed C57BL/6 mice. Collectively, GA micelles can enhance penetration of LA to the epidermis mainly via the hair follicles following topical application, and reduce skin pigmentation.


Assuntos
Glycyrrhiza , Micelas , Animais , Chalconas , Portadores de Fármacos , Ácido Glicirrízico , Melaninas , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Pele
6.
Chem Biol Interact ; 350: 109699, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648814

RESUMO

Despite extensive efforts, cancer is still often considered as an incurable disease and initiation of novel drug development programs is crucial to improve the prognosis and clinical outcome of patients. One of the major approaches in designing the novel cancer drugs has historically comprised studies of natural agents with diverse anticancer properties. As only a marginal part of natural compounds has been investigated, this approach still represents an attractive source of new potential antitumor molecules. In this review article, different anticancer effects of plant-derived chalcone, butein, are discussed, including its growth inhibitory action, proapoptotic, antiangiogenic and antimetastatic activities in a variety of cancer cells. The molecular mechanisms underlying these effects are presented in detail, revealing interactions of butein with multiple cellular targets (Bcl-2/Bax, caspases, STAT3, cyclins, NF-κB, COX-2, MMP-9, VEGF/R etc.) and regulation of a wide range of intracellular signal transduction pathways. These data altogether allow a good basis for initiating further in vivo studies as well as clinical trials. Along with the efforts to overcome low bioavailability issues generally characteristic to plant metabolites, butein can be considered as a potential lead compound for safe and more efficient cancer drugs in the future.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Chalconas/farmacologia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anticarcinógenos/química , Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Chalconas/química , Chalconas/farmacocinética , Quimioprevenção , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Nanotecnologia , Oxirredução
7.
Molecules ; 26(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34641467

RESUMO

Sulfonamidochalcones continue to assert themselves as versatile synthetic intermedi-ates and several articles continue to appear in literature describing their synthesis, chemical transformation and biological properties. These compounds are not only of interest from the medicinal chemistry context, their conformations and crystalline structures also continue to attract attention to explore non-covalent (intramolecular and intermolecular) interactions, control molecular conformations, and improve their physicochemical and optical properties. Despite an exhaustive list of examples of the ring-A sulfonamide-appended chalcones described in the literature, there is no com-prehensive review dedicated to their synthesis, structural and biological properties. This review focuses attention on the synthesis, structure and biological properties of the ring-A sulfonamide-appended chalcones (o/m/p-sulfonamidochalcones) as well as their potential as non-linear optical materials.


Assuntos
Chalconas/química , Chalconas/farmacologia , Desenho de Fármacos , Sulfonamidas/química , Animais , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Química Farmacêutica , Humanos , Inibidores de Fosfodiesterase/farmacologia , Relação Estrutura-Atividade
8.
Anal Chim Acta ; 1178: 338807, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482879

RESUMO

In this work, we have designed and synthesized a new fluorescent molecular probe, DPY comprising of pyrene-diacetylpyridine conjugate, which was found to be sensitive to hydrazine as well as protonation. DPY is characterised by a strong emission both in solution (λem = 530 nm) as well as in solid state (λem = 610 nm), attributed to intramolecular charge-transfer. The probe responds to hydrazine with a ratiometric fluorescence emission change from yellow to blue, due to chalcone cyclisation reaction of α, ß-unsaturated carbonyl group resulting in the pyrazoline compound, DPY-Hy, imparting a strong greenish-blue emission in solution. Further, the strong fluorescence emission of DPY in powder and thin film was quenched upon exposure to TFA, and revived upon exposure to TEA. For developing on-site detection protocol, when DPY was drop-casted on nonfluorescent silica plate a vivid naked-eye colour change from orange-red to dark blue was realized. Interestingly, in the aggregated state, DPY exhibited a broad range emission from green to orange in a mixed solvent system of THF:H2O. A plausible explanation of the photophysical events is substantiated with theoretical calculations.


Assuntos
Chalcona , Chalconas , Corantes Fluorescentes , Hidrazinas , Pirenos
9.
Medicina (Kaunas) ; 57(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34577821

RESUMO

Background and Objectives: Gouty arthritis is an acute inflammatory response caused by the precipitation of monosodium urate (MSU) crystals in joints. The triggering of MSU leads to increased production of inflammatory cytokines, such as interleukin-1ß, which in turn lead to the formation of macromolecular complexes, referred to as inflammasomes. Thorough characterization of the NLRP3 inflammasome can be used as an indicator of an immune response against harmful stimuli. Cardamonin is a chalcone, mainly found in the seeds of Alpinia katsumadai, and exhibits anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines in vitro. However, the mechanism by which cardamonin treatment alleviates gouty arthritis has yet to be fully elucidated. Materials and Methods: In vitro or in vivo models were used to study whether cardamonimn inhibited NLRP3 inflammasome activation or suppressed gouty inflammation. Results: In the current study, we determined that most NLRP3 was released passively after MSU stimulation, and this release of NLRP3 promoted caspase-1 activation and IL-1ß secretion. Cardamonin was shown to decrease both the activity of caspase-1 and secretion of IL-1ß in J774A.1 macrophage cells subjected to MSU stimulation. Cardamonin was also shown to attenuate the production of COX-2 in MSU-stimulated J774A.1 macrophage cells. Finally, cardamonin reduced the thickness of the synovial lining and the infiltration of gouty arthritis in a rat model. Conclusions: Overall, cardamonin significantly attenuated IL-1ß secretion, caspase-1 activity, and COX-2 production stimulated by MSU. These findings provide new insights into the molecular mechanisms underlying the effects of cardamonin treatment for gouty arthritis.


Assuntos
Artrite Gotosa , Chalconas , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Chalconas/farmacologia , Chalconas/uso terapêutico , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Ácido Úrico
10.
Front Cell Infect Microbiol ; 11: 680127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527599

RESUMO

Since the first reported case caused by the novel coronavirus SARS-CoV-2 infection in Wuhan, COVID-19 has caused serious deaths and an ongoing global pandemic, and it is still raging in more than 200 countries and regions around the world and many new variants have appeared in the process of continuous transmission. In the early stage of the epidemic prevention and control and clinical treatment, traditional Chinese medicine played a huge role in China. Here, we screened out six monomer compounds, including artemether, artesunate, arteannuin B, echinatin, licochalcone B and andrographolide, with excellent anti-SARS-CoV-2 and anti-GX_P2V activity from Anti-COVID-19 Traditional Chinese Medicine Compound Library containing 389 monomer compounds extracted from traditional Chinese medicine prescriptions "three formulas and three drugs". Our discovery preliminary proved the stage of action of those compounds against SARS-CoV-2 and provided inspiration for further research and clinical applications.


Assuntos
COVID-19 , SARS-CoV-2 , Artemeter , Artemisininas , Artesunato , Chalconas , Diterpenos , Humanos
11.
J Agric Food Chem ; 69(40): 11926-11936, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34587738

RESUMO

People are at high risk of exposure to endogenous and exogenous acrolein (ACR). ACR can cause a multitude of illnesses, including cardiovascular disease, Alzheimer's disease, and diabetes. In this study, we investigated the reaction pathway of cardamonin (CAR) or alpinetin (ALP) with ACR and the interconversion of CAR and ALP in vitro at 37 °C in phosphate-buffered saline using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, ACR adducts of CAR, ALP, and their metabolites, for example, CAR-ACR-1, ALP-ACR, mono-ACR-pinocembrin chalcone (PIN-ACR), and mono- and di-ACR-naringenin (NAR-ACR and NAR-2ACR), were detected in urine samples, but only CAR-ACR-1 and ALP-ACR were detected in fecal samples from the CAR- and ALP-treated mouse groups using ultraperformance liquid chromatography-MS/MS, respectively. Quantitative analyses showed that CAR, ALP, and their metabolites markedly scavenged ACR in a dose-dependent manner in vivo. Furthermore, we also found that the metabolites of CAR or ALP remained and promoted the ACR-trapping ability.


Assuntos
Acroleína , Espectrometria de Massas em Tandem , Animais , Chalconas , Cromatografia Líquida , Flavanonas , Camundongos
12.
Fitoterapia ; 154: 105029, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34506872

RESUMO

Four new chalchonoid trimers, named cochinchinenins N-Q (1-4), along with a pair of known enantiomers (5-6), were isolated from the total phenolic extract of Chinese dragon's blood (the red resin of Dracaena cochinchinensis). The planar structures of 1-4 were elucidated by extensive spectroscopic analysis including HRESIMS and 1D/2D NMR. The absolute configurations of new compounds were established by ECD data. Compound 1 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 value of 11.5 ± 1.7 µM.


Assuntos
Chalconas/farmacologia , Dracaena/química , Microglia/efeitos dos fármacos , Extratos Vegetais/química , Animais , Linhagem Celular , Chalconas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Óxido Nítrico , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Resinas Vegetais/química
13.
Molecules ; 26(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34500755

RESUMO

Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1-15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of -7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.


Assuntos
Antibacterianos/farmacologia , Chalconas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pirróis/farmacologia , Antibacterianos/química , Chalconas/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirróis/química , Relação Estrutura-Atividade
14.
Adv Clin Exp Med ; 30(11): 1195-1203, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510844

RESUMO

BACKGROUND: Oxidative stress has been reported to be an early factor in the development of cataracts. Echinatin (Ech) is an active ingredient of licorice that exhibits antioxidant effects. OBJECTIVES: To investigate the effects of Ech on oxidative stress-induced lens epithelial cell (LEC) damage. MATERIAL AND METHODS: Human lens epithelial B3 cells (HLECs) were exposed to hydrogen peroxide (H2O2) and were pretreated with or without Ech. For rescue experiments, ML385, an inhibitor of the Nrf2 pathway, was added into the medium. RESULTS: Echinatin reversed the H2O2-induced reduction of cell viability in B3 cells. Additionally, H2O2 induced oxidative stress, evidenced by an increase of reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and a decrease in superoxide dismutase (SOD) and catalase (CAT) levels, which could be abolished by Ech. Echinatin treatment also reduced HLEC apoptosis induced by H2O2. In addition, Ech pretreatment promoted Bcl-2 expression, and suppressed Bax and caspase-3 expression levels, in H2O2-treated B3 cells. Moreover, H2O2 significantly reduced Nrf2 nuclear localization, as well as HO-1 and NQO1 expression, which could be reversed by Ech. Inhibition of Nrf2 by ML385 aggravated H2O2-induced oxidative damage and apoptosis in HLECs, and the protective effects of Ech on H2O2-induced oxidative damage and apoptosis could be restored by ML385. CONCLUSIONS: Echinatin mitigates H2O2-induced oxidative damage and apoptosis in HLECs via the Nrf2/HO-1 pathway, suggesting that Ech may be a potential drug for the treatment of cataracts.


Assuntos
Peróxido de Hidrogênio , Fator 2 Relacionado a NF-E2 , Antioxidantes/farmacologia , Apoptose , Sobrevivência Celular , Chalconas , Células Epiteliais/metabolismo , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio
15.
Phytother Res ; 35(11): 6270-6280, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34486187

RESUMO

Licochalcone A (Lico A) is a natural flavonoid belonging to the class of substituted chalcone that has various biological effects. Mast cells (MCs) are innate immune cells that mediate hypersensitivity and pseudo-allergic reactions. MAS-related GPR family member X2 (MRGPRX2) on MCs has been recognized as the main receptor for pseudo-allergic reactions. In this study, we investigated the anti-pseudo-allergy effect of Lico A and its underlying mechanism. Substance P (SP), as an MC activator, was used to establish an in vitro and in vivo model of pseudo-allergy. The in vivo effect of Lico A was investigated using passive cutaneous anaphylaxis (PCA) and active systemic allergy, along with degranulation, Ca2+ influx in vitro. SP-induced laboratory of allergic disease 2 (LAD2) cell mRNA expression was explored using RNA-seq, and Lico A inhibited LAD2 cell activation by reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence staining. Lico A showed an inhibitory effect on SP-induced MC activation and pseudo-allergy both in vitro and in vivo. The nuclear factor (NF)-κB pathway is involved in MRGPRX2 induced MC activation, which is inhibited by Lico A. In conclusion, Lico A inhibited the pseudo-allergic reaction mediated by MRGPRX2 by blocking NF-κB nuclear migration.


Assuntos
Chalconas , Hipersensibilidade , Degranulação Celular , Chalconas/farmacologia , Família , Humanos , Hipersensibilidade/tratamento farmacológico , Mastócitos , NF-kappa B , Proteínas do Tecido Nervoso , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos
16.
Comput Biol Chem ; 94: 107565, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34474201

RESUMO

A series of novel urea, sulfamide and N,N-dipropargyl substituted benzylamines were synthesized from dihydrochalcones. The synthesized compounds were evaluated for their cholinesterases and carbonic anhydrase inhibitory actions. The known dihydrochalcones were converted into four new benzylamines via reductive amination. N,N-Dipropargylamines, ureas and sulfamides were synthesized following the reactions of benzylamines with propargyl bromide, N,N-dimethyl sulfamoyl chloride and N,N-dimethyl carbamoyl chloride. The novel substituted benzylamines derived from dihydrochalcones were evaluated against some enzymes such as human erythrocyte carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The novel substituted benzylamines derived from dihydrochalcones exhibited Ki values in the range of 0.121-1.007 nM on hCA I, and 0.077-0.487 nM on hCA II closely related to several pathological processes. On the other hand, Ki values were found in the range of 0.112-0.558 nM on AChE, 0.061-0.388 nM on BChE. As a result, novel substituted benzylamines derived from dihydrochalcones showed potent inhibitory profiles against indicated metabolic enzymes. In addition, Induced-Fit Docking (IFD) simulations and ADME prediction studies have also been carried out to elucidate the inhibition mechanisms and drug-likeness of the synthesized compounds. Therefore, these results can make significant contributions to the treatment of some global diseases, especially Alzheimer's diseases and glaucoma, and the development of new drugs.


Assuntos
Benzilaminas/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Chalconas/farmacologia , Inibidores da Colinesterase/farmacologia , Acetilcolinesterase/metabolismo , Animais , Benzilaminas/síntese química , Benzilaminas/química , Butirilcolinesterase/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/metabolismo , Chalconas/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Electrophorus , Cavalos , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
17.
PLoS One ; 16(9): e0257808, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582495

RESUMO

The Ultraviolet-visible (UV-Vis) spectra indicate that anthracenyl chalcones (ACs) have high maximum wavelengths and good transparency windows for optical applications and are suitable for optoelectronic applications owing to their HOMO-LUMO energy gaps (2.93 and 2.76 eV). Different donor substituents on the AC affect their dipole moments and nonlinear optical (NLO) responses. The positive, negative, and neutral electrostatic potential regions of the molecules were identified using molecular electrostatic potential (MEP). The stability of the molecule on account of hyperconjugative interactions and accompanying charge delocalization was analyzed using natural bond orbital (NBO) analysis. Open and closed aperture Z-scans were performed using a continuous-wave frequency-doubled diode-pumped solid-state (DPSS) laser to measure the nonlinear absorption and nonlinear refractive index coefficients, respectively. The valley-to-peak profile of AC indicated a negative nonlinear refractive index coefficient. The obtained single crystals possess reverse saturation absorption due to excited-state absorption. The structural and nonlinear optical properties of the molecules have been discussed, along with the role of anthracene substitution for enhancing the nonlinear optical properties. The calculated third-order susceptibility value was 1.10 x10-4 esu at an intensity of 4.1 kW/cm2, higher than the reported values for related chalcone derivatives. The NLO response for both ACs offers excellent potential in optical switching and limiting applications.


Assuntos
Antracenos/química , Chalconas/química , Compostos de Anéis Fundidos/química , Cristalografia por Raios X , Teoria da Densidade Funcional , Estrutura Molecular , Teoria Quântica
18.
Int J Mol Sci ; 22(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34502529

RESUMO

Natural chalcones possess antitumor properties and play a role as inducers of apoptosis, antioxidants and cytotoxic compounds. We recently reported that novel nitrogen chalcone-based compounds, which were generated in our lab, have specific effects on triple-negative breast cancer cells. However, the outcome of these two new compounds on human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains nascent. Thus, we herein investigated the effects of these compounds (DK-13 and DK-14) on two HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data revealed that these compounds inhibit cell proliferation, deregulate cell-cycle progression and significantly induce cell apoptosis in both cell lines. Furthermore, the two chalcone compounds cause a significant reduction in the cell invasion ability of SKBR3 and ZR75 cancer cells. In parallel, we found that DK-13 and DK-14 inhibit colony formation of both cell lines in comparison to their matched controls. On the other hand, we noticed that these two compounds can inhibit angiogenesis in the chorioallantoic membrane model. The molecular pathway analysis of chalcone compounds exposed cells revealed that these compounds inhibit the expression of both JNK1/2/3 and ERK1/2, the major plausible molecular pathways behind these events. Our findings implicate that DK-13 and DK-14 possess effective chemotherapeutic outcomes against HER2-positive breast cancer via the ERK1/2 and JNK1/2/3 signaling pathways.


Assuntos
Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chalconas/química , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Nitrogênio/química
19.
Int J Mol Sci ; 22(17)2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34502528

RESUMO

Flavonoids, including chalcones, are more stable and bioavailable in the form of glycosylated and methylated derivatives. The combined chemical and biotechnological methods can be applied to obtain such compounds. In the present study, 2'-hydroxy-2-methylchalcone was synthesized and biotransformed in the cultures of entomopathogenic filamentous fungi Beauveria bassiana KCH J1.5, Isaria fumosorosea KCH J2 and Isaria farinosa KCH J2.6, which have been known for their extensive enzymatic system and ability to perform glycosylation of flavonoids. As a result, five new glycosylated dihydrochalcones were obtained. Biotransformation of 2'-hydroxy-2-methylchalcone by B. bassiana KCH J1.5 resulted in four glycosylated dihydrochalcones: 2'-hydroxy-2-methyldihydrochalcone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside, 2',3-dihydroxy-2-methyldihydrochalcone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside, 2'-hydroxy-2-hydroxymethyldihydrochalcone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside, and 2',4-dihydroxy-2-methyldihydrochalcone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside. In the culture of I. fumosorosea KCH J2 only one product was formed-3-hydroxy-2-methyldihydrochalcone 2'-O-ß-d-(4″-O-methyl)-glucopyranoside. Biotransformation performed by I. farinosa KCH J2.6 resulted in the formation of two products: 2'-hydroxy-2-methyldihydrochalcone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside and 2',3-dihydroxy-2-methyldihydrochalcone 3'-O-ß-d-(4″-O-methyl)-glucopyranoside. The structures of all obtained products were established based on the NMR spectroscopy. All products mentioned above may be used in further studies as potentially bioactive compounds with improved stability and bioavailability. These compounds can be considered as flavor enhancers and potential sweeteners.


Assuntos
Beauveria/metabolismo , Chalconas/biossíntese , Cordyceps/metabolismo , Biotransformação , Glicosilação
20.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443487

RESUMO

The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound 12e exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC50 values of 1.38, 5.34, and 5.21 µM, respectively. The structure-activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound 12e inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound 12e could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound 12e might be a valuable lead compound for the development of anticancer agents.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Chalconas/síntese química , Chalconas/farmacologia , Desenho de Fármacos , Quinolinas/síntese química , Quinolinas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Humanos , Quinolinas/química , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
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