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1.
Int J Mol Sci ; 23(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36555814

RESUMO

Radiation exposure causes acute damage to hematopoietic and immune cells. To date, there are no radioprotectors available to mitigate hematopoietic injury after radiation exposure. Gamma-tocotrienol (GT3) has demonstrated promising radioprotective efficacy in the mouse and nonhuman primate (NHP) models. We determined GT3-mediated hematopoietic recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques divided into two groups received either vehicle or GT3, 24 h prior to TBI. Four animals in each treatment group were exposed to either 4 or 5.8 Gy TBI. Flow cytometry was used to immunophenotype the bone marrow (BM) lymphoid cell populations, while clonogenic ability of hematopoietic stem cells (HSCs) was assessed by colony forming unit (CFU) assays on day 8 prior to irradiation and days 2, 7, 14, and 30 post-irradiation. Both radiation doses showed significant changes in the frequencies of B and T-cell subsets, including the self-renewable capacity of HSCs. Importantly, GT3 accelerated the recovery in CD34+ cells, increased HSC function as shown by improved recovery of CFU-granulocyte macrophages (CFU-GM) and burst-forming units erythroid (B-FUE), and aided the recovery of circulating neutrophils and platelets. These data elucidate the role of GT3 in hematopoietic recovery, which should be explored as a potential medical countermeasure to mitigate radiation-induced injury to the hematopoietic system.


Assuntos
Células-Tronco Hematopoéticas , Vitamina E , Camundongos , Animais , Macaca mulatta , Vitamina E/farmacologia , Cromanos/farmacologia , Irradiação Corporal Total
2.
J Org Chem ; 87(23): 15863-15887, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36373006

RESUMO

ortho-Quinone methides (o-QMs) underwent formal [4 + 2]-cycloaddition reactions with arylallenes regioselectively at the styrenyl olefin to furnish the corresponding 3-methylene-2-arylchromans in moderate to good yields (up to 88%). When R ≠ H, the reactions also proceeded with moderate stereoselectivity (up to 5:1) which was governed by the nature of the R group. The 3-methylene-2-arylchromans could serve as common intermediates for further functionalization including epoxidation, oxidative cleavage/Baeyer-Villiger oxidation, Riley oxidation, acid-catalyzed rearrangement, and Pd-catalyzed cross-coupling reactions to furnish the corresponding derivatives in moderate to good yields.


Assuntos
Cromanos , Indolquinonas , Reação de Cicloadição , Oxirredução
3.
Int J Mol Sci ; 23(19)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36233044

RESUMO

Recent interest in the antioxidant capacity of foods and beverages is based on the established medical knowledge that antioxidants play an essential role in counteracting the damaging effects of free radicals, preventing human neurodegenerative diseases, cardiovascular disorders, and even cancer. At the same time, there is no "the method" that uniquely defines the antioxidant capacity of substances; moreover, the question of interrelation between results obtained by different experimental techniques is still open. In this work, we consider the trolox equivalent antioxidant capacity (TEAC) values obtained by electron paramagnetic resonance (EPR) spectroscopy and ultraviolet-visible (UV-vis) spectroscopy using the classic objects for such studies as an example: red, rosé, and white wine samples. Based on entirely different physical principles, these two methods give values that are not so simply interrelated; this creates a demand for machine learning as a suitable tool for revealing quantitative correspondence between them. The consideration consists of an approximate correlation-based analytical model for the key argument (i.e., TEACEPR) with subsequent adjustment by machine learning-based processing utilizing the CatBoost algorithm with the usage of auxiliary chemical data, such as the total phenolic content and color index, which cannot be accurately described by analytical expressions.


Assuntos
Antioxidantes , Cromanos , Antioxidantes/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Humanos , Aprendizado de Máquina
4.
Molecules ; 27(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36234726

RESUMO

Vitamin E, a collection of lipophilic phenolic compounds based on chroman-6-ol, has a rich and fascinating oxidative chemistry involving a range of intermediate forms, some of which are proposed to be important in its biological functions. In this review, the available electrochemical and spectroscopic data on these oxidized intermediates are summarized, along with a discussion on how their lifetimes and chemical stability are either typical of similar phenolic and chroman-6-ol derived compounds, or atypical and unique to the specific oxidized isomeric form of vitamin E. The overall electrochemical oxidation mechanism for vitamin E can be summarized as involving the loss of two-electrons and one-proton, although the electron transfer and chemical steps can be controlled to progress along different pathways to prolong the lifetimes of discreet intermediates by modifying the experimental conditions (applied electrochemical potential, aqueous or non-aqueous solvent, and pH). Depending on the environment, the electrochemical reactions can involve single electron transfer (SET), proton-coupled electron transfer (PCET), as well as homogeneous disproportionation and comproportionation steps. The intermediate species produced via chemical or electrochemical oxidation include phenolates, phenol cation radicals, phenoxyl neutral radicals, dications, diamagnetic cations (phenoxeniums) and para-quinone methides. The cation radicals of all the tocopherols are atypically long-lived compared to the cation radicals of other phenols, due to their relatively weak acidity. The diamagnetic cation derived from α-tocopherol is exceptionally long-lived compared to the diamagnetic cations from the other ß-, γ- and δ-isomers of vitamin E and compared with other phenoxenium cations derived from phenolic compounds. In contrast, the lifetime of the phenoxyl radical derived from α-tocopherol, which is considered to be critical in biological reactions, is typical for what is expected for a compound with its structural features. Over longer times via hydrolysis reactions, hydroxy para-quinone hemiketals and quinones can be formed from the oxidized intermediates, which can themselves undergo reduction processes to form intermediate anion radicals and dianions. Methods for generating the oxidized intermediates by chemical, photochemical and electrochemical methods are discussed, along with a summary of how the final products vary depending on the method used for oxidation. Since the intermediates mainly only survive in solution, they are most often monitored using UV-vis spectroscopy, FTIR or Raman spectroscopies, and EPR spectroscopy, with the spectroscopic techniques sometimes combined with fast photoinitiated excitation and time-resolved spectroscopy for detection of short-lived species.


Assuntos
Fenol , Vitamina E , Benzoquinonas , Cromanos , Espectroscopia de Ressonância de Spin Eletrônica , Oxirredução , Fenóis/química , Prótons , Solventes/química , Tocoferóis , alfa-Tocoferol/química
5.
Org Biomol Chem ; 20(41): 8136-8144, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36218163

RESUMO

A new method for the stereoselective metal-, additive- and oxidant-free Friedel-Crafts-type halo-carbocyclization of N- and O-tethered arene-olefin substrates is reported, involving reaction with a suitable electrophilic halogenating reagent (NXS/DCDMH) in hexafluoroisopropanol. All halo (X = Br, I, Cl)-functionalized tetrahydroquinolines and chromans were obtained in excellent yields and with high levels of diastereocontrol (dr = >99 : 1), and these products were successfully transformed into synthetically useful compounds such as dihydroquinolines and partial or full azahelicene compounds.


Assuntos
Alcenos , Quinolinas , Alcenos/química , Catálise , Cromanos/química , Quinolinas/química
6.
Molecules ; 27(20)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36296640

RESUMO

An efficient and straightforward approach for the synthesis of carbamoylated chroman-4-ones has been well-developed. The reaction is triggered through the generation of carbamoyl radicals from oxamic acids under metal-free conditions, which subsequently undergoes decarboxylative radical cascade cyclization on 2-(allyloxy)arylaldehydes to afford various amide-containing chroman-4-one scaffolds with high functional group tolerance and a broad substrate scope.


Assuntos
Cromanos , Ácido Oxâmico , Ciclização , Amidas
7.
Contrast Media Mol Imaging ; 2022: 7445042, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072638

RESUMO

The effect of the TGF-ß pathway-based pituitary tumor of rats on the GH3 cell line after intervention with different concentrations of troglitazone (TGZ) is explored. The CH3 cell line of 24 clean male SD rats with pituitary adenoma is selected. The cells are divided into a blank contrast set and an experimental set. The experimental set is divided into different TGZ concentration sets, including 1 × 10-3 TGZ set, 1 × 10-4 TGZ set, and 1 × 10-5 TGZ set. The cell proliferation is detected by the CCK-8 method, the protein expressions of CD147, TGF-ß1, and MMP-9 are detected by the western blot method, and the relative mRNA expressions of CD147, TGF-ß1, and MMP-9 are detected by the qRT-PCR method. The expression levels of CD147, TGF-ß1, and MMP-9 in CH3 cells of pituitary adenoma rats are notoriously lower, while the expression of CD147, TGF-31, and MMP-9 could be reduced by TGZ acting on the GH3 cell line. The specific mechanism of action of this effect on the invasive ability of GH3 cell lines is multifaceted, suggesting that peroxisome proliferator activator-receptor (PPAR-γ) agonists have good clinical application prospects in tumor therapy and can provide new targets and approaches for tumor drug therapy.


Assuntos
Neoplasias Hipofisárias , Tiazolidinedionas , Animais , Linhagem Celular , Cromanos/farmacologia , Masculino , Metaloproteinase 9 da Matriz , Neoplasias Hipofisárias/genética , Ratos , Ratos Sprague-Dawley , Tiazolidinedionas/farmacologia , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta1 , Troglitazona
8.
Mol Immunol ; 151: 126-133, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36126500

RESUMO

γ-Tocotrienol (GT3), a member of the vitamin E family, is well known for its medicinal value in clinical treatments. However, the role of GT3 in T helper 17 (Th17)/regulatory T cell (Treg) differentiation and function is not fully understood. Here, we demonstrated that GT3 suppressed Th17 differentiation in vitro by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation in the interleukin 6 (IL-6)/Janus kinase (JAK)/STAT3 signaling pathway. GT3 also inhibited HIF1A expression in Th17 metabolism. Additionally, we showed that GT3 treatment inhibited disease aggravation in an imiquimod (IMQ)-induced psoriasis-like mouse model by reducing the percentage of Th17 cells in the spleen in vivo. The findings of this study demonstrated the effects of GT3 on Th17 cells through the STAT3 signaling pathway.


Assuntos
Janus Quinases , Fator de Transcrição STAT3 , Animais , Diferenciação Celular , Cromanos , Imiquimode/farmacologia , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células Th17 , Vitamina E/análogos & derivados , Vitamina E/metabolismo , Vitamina E/farmacologia
9.
Molecules ; 27(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36014320

RESUMO

In this paper, the organocatalytic asymmetric Michael addition/hemiketalization cascade reactions between hydroxymaleimides and 2-hydroxynitrostyrenes were developed, which provided a new protocol for building a chiral ring-fused chroman skeleton. This squaramide-catalyzed cascade reaction provided chiral chroman-fused pyrrolidinediones with three contiguous stereocenters in good to high yields (up to 88%), with excellent diastereoselectivities (up to >20:1 dr) and enantioselectivities (up to 96% ee) at -16 °C. Moreover, a scale-up synthesis was also carried out, and a possible reaction mechanism was proposed.


Assuntos
Cromanos , Succinimidas , Catálise , Estereoisomerismo
10.
Arh Hig Rada Toksikol ; 73(2): 158-168, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35792769

RESUMO

Strawberry tree (Arbutus unedo L.) honey (STH), also known as "bitter honey", is a traditional medicine widely used in the Mediterranean area. Regardless of geographical origin, it usually has a very high content of phenolic compounds and strong antioxidant capacity. Yet, little is still known about the effects of STH, its phenolic extract (STHE), and its main bioactive compound - homogentisic acid (HGA) - at the cell level. The aim of this study was to estimate total phenolic content, DPPH radical scavenging activity, and ferric reducing antioxidant power of STH made in Croatia and investigate cytotoxic and pro-oxidative effects of STH, STHE and HGA on three human cell lines: tongue squamous cell carcinoma (CAL 27), hepatocellular carcinoma (HepG2), and epithelial colorectal adenocarcinoma cells (Caco-2) cells. These substances were tested at four concentrations (0.5-5× average human daily intake of STH) and over 30 min and 1 and 2 h. Croatian STH had a total phenolic content of 1.67 g gallic acid equivalents (GAE) per kg of honey, DPPH radical scavenging activity of 2.96 mmol Trolox equivalents (TE) per kg of honey, and ferric reducing antioxidant power (FRAP) of 13.5 mmol Fe2+ per kg of honey. Our results show no clear and consistent time- or concentration-dependent cytotoxicity in any of the cell lines. ROS levels in all the three cell types at almost all exposure times were not significantly higher than control. The most important observation is that the tested substances have low cytotoxicity and high biocompatibility, regardless of concentration, which is a good starting point for further research of their biological effects in other models.


Assuntos
Antineoplásicos , Ericaceae , Ácido Homogentísico , Mel , Extratos Vegetais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo , Células CACO-2 , Carcinoma Hepatocelular , Carcinoma de Células Escamosas , Cromanos , Neoplasias Colorretais , Ericaceae/química , Ácido Gálico , Células Hep G2 , Ácido Homogentísico/farmacologia , Humanos , Ferro/química , Neoplasias Hepáticas , Fenóis/farmacologia , Picratos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio , Neoplasias da Língua , Árvores/química
11.
Molecules ; 27(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35889502

RESUMO

Vitamin E consists of a group of compounds including α- ß- γ- and δ-tocopherols and α- ß- γ- and δ-tocotrienols, containing the chroman-6-ol system. The recognition of the structural and dynamic properties of this system, present in all vitamers, seems to be important for the full explanation of the mechanism of the biological activity of vitamin E. This paper presents results of the structural analysis of the chosen 6-chromanyl ethereal derivatives using experimental (13 C NMR-in solution and solid state, as well as variable temperature experiments; single crystal X-ray diffraction) and theoretical (DFT) methods. For one of the studied compounds, 2,2,5,7,8-pentamethyl-6-((tetrahydro-2H-pyran-2-yl)oxy) chroman, the splitting of some signals was observed in the 13C dynamic NMR spectra. This observation was explained by the application of a conformational analysis and subsequent DFT optimization, followed by the calculation of NMR properties.


Assuntos
Éter , Éteres , Cromanos , Etil-Éteres , Espectroscopia de Ressonância Magnética/métodos , Vitamina E/química
12.
Org Lett ; 24(29): 5468-5473, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35856291

RESUMO

The 1,1a,2,7b-tetrahydrocyclopropa[c]chromene, arising from fusion of chromane and cyclopropane rings is the core of medicinally relevant compounds. Engaging sulfoxonium ylides in enantioselective aminocatalytic reactions for the first time, a convenient entry to this scaffold is presented. Several ring-fused derivatives were obtained in moderate-to-good yields and enantioselectivities and with perfect diastereoselectivity at the cyclopropane, using an α,α-diphenylprolinol aminocatalyst. The versatility of the hemiacetal moiety in the products was leveraged to effect various synthetic manipulations.


Assuntos
Cromanos , Ciclopropanos , Benzopiranos , Ciclopropanos/química , Estereoisomerismo
13.
Chem Biodivers ; 19(8): e202200304, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35821618

RESUMO

A series of novel spiro-[chromane-2,4'-piperidin]-4(3H)-one derivatives were designed, synthesized and structures were confirmed by analytical methods, viz., 1 H-NMR, 13 C-NMR and mass spectrometry. The synthetic derivatives were evaluated for their anti-tuberculosis (anti-TB) activity against Mycobacterium tuberculosis (Mtb) strain H37Ra. Among all the evaluated Compounds, PS08 exhibited significant inhibition with MIC value of 3.72 µM while MIC values of the remaining Compounds ranged from 7.68 to 230.42 µM in comparison to the standard drug INH (MIC 0.09 µM). The two most active Compounds however showed acute cytotoxicity towards the human MRC-5 lung fibroblast cell lines. The in silico ADMET profiles of the titled Compounds were predicted and found within the prescribed limits of the Lipinski and Jorgenson rules. Molecular docking study of the notably active Compound (PS08) was also carried out after performing validation in order to understand the putative binding position of the test ligand at the active site of selected target protein Mtb tyrosine phosphatase (PtpB).


Assuntos
Antituberculosos , Mycobacterium tuberculosis , Cromanos , Desenho de Fármacos , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
14.
Int J Mol Sci ; 23(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35563033

RESUMO

The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated GI recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques were divided into two groups; eight received vehicle and eight GT3 24 h prior to 12 Gy TBI. Proximal jejunum was assessed for structural injuries and crypt survival on day 4 and 7. Apoptotic cell death and crypt cell proliferation were assessed with TUNEL and Ki-67 immunostaining. Irradiation induced significant shortening of the villi and reduced mucosal surface area. GT3 induced an increase in crypt depth at day 7, suggesting that more stem cells survived and proliferated after irradiation. GT3 did not influence crypt survival after irradiation. GT3 treatment caused a significant decline in TUNEL-positive cells at both day 4 (p < 0.03) and 7 (p < 0.0003). Importantly, GT3 induced a significant increase in Ki-67-positive cells at day 7 (p < 0.05). These data suggest that GT3 has radioprotective function in intestinal epithelial and crypt cells. GT3 should be further explored as a prophylactic medical countermeasure for radiation-induced GI injury.


Assuntos
Síndrome Aguda da Radiação , Cromanos , Protetores contra Radiação , Vitamina E , Síndrome Aguda da Radiação/tratamento farmacológico , Síndrome Aguda da Radiação/prevenção & controle , Animais , Cromanos/uso terapêutico , Modelos Animais de Doenças , Intestinos/patologia , Intestinos/efeitos da radiação , Antígeno Ki-67 , Macaca mulatta , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Vitamina E/análogos & derivados , Vitamina E/uso terapêutico
15.
Chemistry ; 28(27): e202200224, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35298095

RESUMO

Cooperative enamine-metal Lewis acid catalysis has emerged as a powerful tool to construct carbon-carbon and carbon-heteroatom bond forming reactions. A concise synthetic method for asymmetric synthesis of chromans from cyclohexanones and salicylaldehydes has been developed to afford tricyclic chromans containing three consecutive stereogenic centers in good yields (up to 87 %) and stereoselectivity (up to 99 % ee and 11 : 1 : 1 dr). This difficult organic transformation was achieved through bifunctional enamine-metal Lewis acid catalysis. It is believed that the strong activation of the salicylaldehydes through chelating to the metal Lewis acid and the bifunctional nature of the catalyst accounts for the high yields and enantioselectivity of the reaction. The absolute configurations of the chroman products were established through X-ray crystallography. DFT calculations were conducted to understand the mechanism and stereoselectivity of this reaction.


Assuntos
Cromanos , Ácidos de Lewis , Carbono , Catálise , Ácidos de Lewis/química , Metais , Estereoisomerismo
16.
Sci Rep ; 12(1): 3387, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35233005

RESUMO

Radiological incidents or terrorist attacks would likely expose civilians and military personnel to high doses of ionizing radiation, leading to the development of acute radiation syndrome. We examined the effectiveness of prophylactic administration of a developmental radiation countermeasure, γ-tocotrienol (GT3), in a total-body irradiation (TBI) mouse model. CD2F1 mice received GT3 24 h prior to 11 Gy cobalt-60 gamma-irradiation. This dose of radiation induces severe hematopoietic acute radiation syndrome and moderate gastrointestinal injury. GT3 provided 100% protection, while the vehicle control group had 100% mortality. Two-dimensional differential in-gel electrophoresis was followed by mass spectrometry and Ingenuity Pathway Analysis (IPA). Analysis revealed a change in expression of 18 proteins in response to TBI, and these changes were reversed with prophylactic treatment of GT3. IPA revealed a network of associated proteins involved in cellular movement, immune cell trafficking, and inflammatory response. Of particular interest, significant expression changes in beta-2-glycoprotein 1, alpha-1-acid glycoprotein 1, alpha-2-macroglobulin, complement C3, mannose-binding protein C, and major urinary protein 6 were noted after TBI and reversed with GT3 treatment. This study reports the untargeted approach, the network, and specific serum proteins which could be translated as biomarkers of both radiation injury and protection by countermeasures.


Assuntos
Síndrome Aguda da Radiação , Protetores contra Radiação , Síndrome Aguda da Radiação/tratamento farmacológico , Animais , Cromanos , Raios gama/efeitos adversos , Glicoproteínas/uso terapêutico , Camundongos , Proteômica , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Vitamina E/análogos & derivados , Irradiação Corporal Total
17.
Biol Pharm Bull ; 45(3): 276-283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35228393

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide. Troglitazone (TGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is a potential antitumor agent. However, the action mechanism of TGZ in lung adenocarcinoma cells has not been completely elucidated. To assess this mechanism and the anticancer effects of TGZ in human lung adenocarcinoma cell lines (A549 and H1975), we investigated the involvement of PPARγ, apoptosis, the mitogen-activated protein kinase (MAPK) pathway, protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, and autophagy. Cell viability was measured using fluorescence-based assays. Apoptotic cells were detected by Hoechst 33342 and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining; protein expression was detected by Western blotting. TGZ inhibited cell proliferation in a dose-dependent manner in both cell lines, and the effect was not suppressed by a PPARγ inhibitor. Additionally, TGZ increased apoptotic cell number and upregulated p38 and c-Jun N-terminal kinase (JNK) phosphorylation; however, p38 and JNK inhibitors did not block TGZ-mediated inhibition of cell proliferation in either cell line. TGZ also upregulated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, whereas an ERK1/2 inhibitor enhanced TGZ-mediated cytotoxicity in A549 cells. Additionally, TGZ increased LC3-II expression, and chloroquine (an autophagy inhibitor) attenuated TGZ-mediated inhibition of cell proliferation. These findings suggest that TGZ-induced inhibition of cell proliferation is PPARγ independent. TGZ-mediated inhibition of cell proliferation was accompanied by apoptosis and independent of the MAPK signaling pathway. These results suggest that TGZ inhibits cell proliferation through autophagy-induced cytotoxicity. This study demonstrated that chemotherapy using TGZ may be effective for lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Tiazolidinedionas , Adenocarcinoma de Pulmão/tratamento farmacológico , Apoptose , Autofagia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Cromanos/farmacologia , Humanos , Tiazolidinedionas/farmacologia , Troglitazona/farmacologia
18.
J Org Chem ; 87(6): 4263-4272, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35234478

RESUMO

Heterocyclic compounds, especially oxygen-containing heterocyclic compounds, are crucial moieties in bioactive compounds and drug leads. Substituted chroman-4-ones are a kind of the most significant structural skeletons. Herein, we report a visible-light-induced dual acylation of alkenes for constructing 3-substituted chroman-4-ones, which undergoes a radical tandem cyclization reaction through carbon-carbon bond cleavage of oxime esters by a nitrogen-centered radical strategy. A series of 3-substituted chroman-4-ones were prepared with up to 86% yield.


Assuntos
Alcenos , Compostos Heterocíclicos , Acilação , Alcenos/química , Carbono/química , Cromanos , Ciclização , Compostos Heterocíclicos/química
19.
Molecules ; 27(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35163847

RESUMO

A novel series of 14 spiropyrrolidines bearing thiochroman-4-one/chroman-4-one, and oxindole/acenaphthylene-1,2-dione moieties were synthesized and characterized by spectroscopic techniques, as well as by three X-ray diffraction studies, corroborating the stereochemistry. Quantum chemical calculations studies, using the DFT approach, were performed to rationalize the stereochemical outcome. These N-heterocycles were evaluated for their antibacterial and antifungal activities against some pathogenic organisms. Several compounds displayed moderate to excellent activity towards the screened microbe strains in the study compared to Amoxicillin (AMX), Ampicillin (AMP), and Amphotericin B. Furthermore, a structural activity relationship (SAR) was established considering the synthesized compounds. Pharmacokinetic studies reveal that these derivatives exhibit an acceptable predictive ADMET profile (Absorption, Distribution, Metabolism, Excretion and Toxicity) and good drug-likeness.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Cromanos/química , Fungos/efeitos dos fármacos , Compostos de Espiro/química , Antibacterianos/química , Antifúngicos/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxindóis/química , Relação Estrutura-Atividade
20.
Curr Mol Pharmacol ; 15(7): 980-986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35100963

RESUMO

BACKGROUND: Breast Cancer is one of the most commonly diagnosed cancers worldwide and a major cause of death among women. Although chemotherapeutic agents remain the keystones in cancer therapy, significant side effects have failed to provide a safe and tolerable treatment for cancer patients. Dietary antioxidant vitamins were extensively investigated over the past years and their relevance in cancer chemotherapy remains to be elucidated. OBJECTIVE: In the current study, we aimed to investigate the anti-proliferative and apoptotic effects of combining γ-tocotrienol, a member of the vitamin E family, with the chemotherapeutic drug etoposide in MCF-7 and MDA-MB-231 breast cancer cell lines. METHODS: The antiproliferative effect of etoposide combined with γ-tocotrienol was measured using MTS viability reagent. The pro-apoptotic effect was elucidated through Cell Death ELISA and dual Annexin V/PI staining followed by flow cytometric analysis. RESULTS: Our results showed that etoposide significantly decreased the cell growth of both cell lines, with MDA-MB-231 cells being more sensitive to etoposide treatment than MCF-7. Moreover, simultaneous treatment of both breast cancer cell lines with low doses of γ-tocotrienol and etoposide induced a synergistic antiproliferative effect (CI<1). Furthermore, the combination therapy significantly increased the percentage of total apoptotic cells in the MDA-MB-231 cell line and the degree of DNA fragmentation as compared to treatment with either compound alone. CONCLUSION: In conclusion, our results provide evidence for the profound anti-tumorigenic effect of combined etoposide and γ-tocotrienol in the breast cancer cell lines.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Cromanos , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Feminino , Humanos , Células MCF-7 , Vitamina E/análogos & derivados , Vitamina E/farmacologia , Vitamina E/uso terapêutico
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