Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 72
Filtrar
1.
J Clin Med ; 13(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39201109

RESUMO

Background/Objectives: Radiography is an essential and low-cost diagnostic method in pulmonary medicine that is used for the early detection and monitoring of lung diseases. An adequate and consistent image quality (IQ) is crucial to ensure accurate diagnosis and effective patient management. This pilot study evaluates the feasibility and effectiveness of the International Atomic Energy Agency (IAEA)'s remote and automated quality control (QC) methodology, which has been tested in multiple imaging centers. Methods: The data, collected between April and December 2022, included 47 longitudinal data sets from 22 digital radiographic units. Participants submitted metadata on the radiography setup, exposure parameters, and imaging modes. The database comprised 968 exposures, each representing multiple image quality parameters and metadata of image acquisition parameters. Python scripts were developed to collate, analyze, and visualize image quality data. Results: The pilot survey identified several critical issues affecting the future implementation of the IAEA method, as follows: (1) difficulty in accessing raw images due to manufacturer restrictions, (2) variability in IQ parameters even among identical X-ray systems and image acquisitions, (3) inconsistencies in phantom construction affecting IQ values, (4) vendor-dependent DICOM tag reporting, and (5) large variability in SNR values compared to other IQ metrics, making SNR less reliable for image quality assessment. Conclusions: Cross-comparisons among radiography systems must be taken with cautious because of the dependence on phantom construction and acquisition mode variations. Awareness of these factors will generate reliable and standardized quality control programs, which are crucial for accurate and fair evaluations, especially in high-frequency chest imaging.

2.
Molecules ; 29(14)2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39064997

RESUMO

The (R,R)-Teth-TsDPEN-Ru(II) complex promoted the one-pot double C=O reduction of α-alkyl-ß-ketoaldehydes through asymmetric transfer hydrogenation/dynamic kinetic resolution (ATH-DKR) under mild conditions. In this process, ten anti-2-benzyl-1-phenylpropane-1,3-diols (85:15 to 92:8 dr) were obtained in good yields (41-87%) and excellent enantioselectivities (>99% ee for all compounds). Notably, the preferential reduction of the aldehyde moiety led to the in situ formation of 2-benzyl-3-hydroxy-1-phenylpropan-1-one intermediates. These intermediates played a crucial role in enhancing both reactivity and stereoselectivity through hydrogen bonding.

3.
Phys Med Biol ; 69(15)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39008980

RESUMO

Objective.Accurate simulation of human tissues is imperative for advancements in diagnostic imaging, particularly in the fields of dosimetry and image quality evaluation. Developing Tissue Equivalent Materials (TEMs) with radiological characteristics akin to those of human tissues is essential for ensuring the reliability and relevance of imaging studies. This study presents the development of a mathematical model and a new toolkit (TEMPy) for obtaining the best composition of materials that mimic the radiological characteristics of human tissues. The model and the toolkit are described, along with an example showcasing its application to obtain desired TEMs.Approach.The methodology consisted of fitting volume fractions of the components of TEM in order to determine its linear attenuation coefficient as close as possible to the linear attenuation coefficient of the reference material. The fitting procedure adopted a modified Least Square Method including a weight function. This function reflects the contribution of the x-ray spectra in the suitable energy range of interest. TEMPy can also be used to estimate the effective atomic number and electron density of the resulting TEM.Main results.TEMPy was used to obtain the chemical composition of materials equivalent to water and soft tissue, in the energy range used in x-ray imaging (10 -150 keV) and for breast tissue using the energy range (5-40 keV). The maximum relative difference between the linear attenuation coefficients of the developed and reference materials was ±5% in the considered energy ranges.Significance.TEMPy facilitates the formulation of TEMs with radiological properties closely mimicking those of real tissues, aiding in the preparation of physical anthropomorphic or geometric phantoms for various applications. The toolkit is freely available to interested readers.


Assuntos
Imagens de Fantasmas , Humanos , Mama/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Modelos Biológicos , Feminino
4.
Org Biomol Chem ; 22(24): 4839-4863, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38819298

RESUMO

Rearranged homoisoflavonoids constitute a unique group of natural products, renowned for their structural diversity and complexity. These compounds, derived from modifications in the 3-benzylchroman skeleton, are categorized into four subclasses: brazilin, caesalpin, protosappanin, and scillascillin homoisoflavonoids. This review examines the advancements in the total synthesis of these complex structures, aiming to highlight the challenges and opportunities encountered. A comparative analysis of the strategies employed thus far to synthesize these compounds provides a comprehensive understanding of the progress in this field.

5.
Mol Biol Rep ; 51(1): 187, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270684

RESUMO

BACKGROUND: Leukemias stand out for being the main type of childhood cancer in the world. Current treatments have strong side effects for patients, and there is still a high rate of development of resistance to multidrug therapy. Previously, our research group developed a structure-activity study with novel synthetic molecules analogous to LQB-278, described as an essential molecule with in vitro antileukemic action. Among these analogs, LQB-461 stood out, presenting more significant antileukemic action compared to its derivative LQB-278, with cytostatic and cytotoxicity effect by apoptosis, inducing caspase-3, and increased sub-G1 phase on cell cycle analysis. METHODS AND RESULTS: Deepening the study of the mechanism of action of LQB-461 in Jurkat cells in vitro, a microarray assay was carried out, which confirmed the importance of the apoptosis pathway in the LQB-461 activity. Through real-time PCR, we validated an increased expression of CDKN1A and BAX genes, essential mediators of the apoptosis intrinsic pathway. Through the extrinsic apoptosis pathway, we found an increased expression of the Fas receptor by flow cytometry, showing the presence of a more sensitive population and another more resistant to death. Considering the importance of autophagy in cellular resistance, it was demonstrated by western blotting that LQB-461 decreased LC-3 protein expression, an autophagic marker. CONCLUSIONS: These results suggest that this synthetic molecule LQB-461 induces cell death by apoptosis in Jurkat cells through intrinsic and extrinsic pathways and inhibits autophagy, overcoming some mechanisms of cell resistance related to this process, which differentiates LQB-461 of other drugs used for the leukemia treatment.


Assuntos
Benzaldeídos , Iminas , Hansenostáticos , Humanos , Quimioterapia Combinada , Células Jurkat , Análise de Dados
6.
JPRAS Open ; 37: 155-162, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37560483

RESUMO

Background: Obesity poses a major risk for cardiovascular diseases, while it is almost a consensus that intra-abdominal adiposity has a more deleterious effect for metabolic syndrome. In this sense, it is speculated that lipectomy or liposuction would be metabolically harmful, as it changes the abdominal-superficial adipose tissue ratio. However, the literature has shown conflicting evidence. Methods: In order to evaluate the possibility of metabolism alteration resulting from body coutouring surgery, a prospective cohort was implemented with 35 patients who underwent abdominoplasty, including some with a history of massive weight loss. Fasting blood glucose, fasting plasma insulin, triglycerides, total cholesterol and fractions were requested preoperatively and in the third postoperative month. The groups were also compared with each other. Results: No statistically significant variation between the exams collected in the preoperative period and those collected after abdominoplasty was found. There was a statistically significant difference in LDL (low-density lipoprotein; p = 0.033) and non-HDL (non-high-density lipoprotein) cholesterol (p = 0.020) between the two control tests of the groups surveyed. There were also differences in comorbidities (p = 0.006) and complications (p <0.001) between the groups. Conclusions: Abdominoplasty was not able of changing tests that assess glycemic and lipid metabolism three months after the operation. Our attention was drawn to the fact that patients who had massive weight loss had better control of LDL cholesterol (p = 0.033) and non-HDL cholesterol (p = 0.020), despite having higher weight and body mass index (p <0.001).

7.
J Nat Prod ; 86(6): 1536-1549, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37257024

RESUMO

Aurones are a small subgroup of flavonoids in which the basic C6-C3-C6 skeleton is arranged as (Z)-2-benzylidenebenzofuran-3(2H)-one. These compounds are structural isomers of flavones and flavonols, natural products reported as potent inhibitors of SARS-CoV-2 replication. Herein, we report the design, synthesis, and anti-SARS-CoV-2 activity of a series of 25 aurones bearing different oxygenated groups (OH, OCH3, OCH2OCH3, OCH2O, OCF2H, and OCH2C6H4R) at the A- and/or B-rings using cell-based screening assays. We observed that 12 of the 25 compounds exhibit EC50 < 3 µM (8e, 8h, 8j, 8k, 8l, 8m, 8p, 8q, 8r, 8w, 8x, and 8y), of which five presented EC50 < 1 µM (8h, 8m, 8p, 8q, and 8w) without evident cytotoxic effect in Calu-3 cells. The substitution of the A- and/or B-ring with OCH3, OCH2OCH3, and OCF2H groups seems beneficial for the antiviral activity, while the corresponding phenolic derivatives showed a significant decrease in the anti-SARS-CoV-2 activity. The most potent compound of the series, aurone 8q (EC50 = 0.4 µM, SI = 2441.3), is 2 to 3 times more effective than the polyphenolic flavonoids myricetin (2) and baicalein (1), respectively. Investigation of the five more active compounds as inhibitors of SARS-CoV-2 3CLpro based on molecular dynamic calculations suggested that these aurones should detach from the active site of 3CLpro, and, probably, they could bind to another SARS-CoV-2 protein target (either receptor or enzyme).


Assuntos
Benzofuranos , COVID-19 , Humanos , SARS-CoV-2 , Benzofuranos/farmacologia , Flavonoides/farmacologia , Flavonoides/química , Antivirais/farmacologia , Inibidores de Proteases/farmacologia , Simulação de Acoplamento Molecular
8.
J Org Chem ; 87(21): 14208-14222, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36251770

RESUMO

The oxo-tethered-Ru(II) precatalyst promoted the one-pot C═C/C═O reduction of chalcones using sodium formate as the hydrogen source in water through asymmetric transfer hydrogenation. Twenty-seven 1,3-diarylpropan-1-ols were obtained in good to excellent yields (up to 96%) and enantiomeric purities (up to 98:2). Our data suggested that the enones are first reduced to the corresponding dihydrochalcones (1,4-selectivity) and then into 1,3-diarylpropan-1-ols (C═O reduction). The stereoelectronic effects of electron-donating and electron-withdrawing groups at the ortho, meta and para positions of both aromatic rings were evaluated. The 2-OH group at the B ring was well tolerated, allowing a straightforward enantioselective synthesis of two flavans through the Mitsunobu cyclization, the antiviral (S)-BW683C and the natural flavan (S)-tephrowatsin E.


Assuntos
Chalcona , Chalconas , Hidrogenação , Estereoisomerismo , Água , Polifenóis , Catálise
9.
Med Phys ; 49(1): 201-218, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34800303

RESUMO

PURPOSE: A Monte Carlo (MC) modeling of single axial and helical CT scan modes has been developed to compute single and accumulated dose distributions. The radiation emission characteristics of an MDCT scanner has been modeled and used to evaluate the dose deposition in infinitely long head and body PMMA phantoms. The simulated accumulated dose distributions determined the approach to equilibrium function, H(L). From these H ( L ) curves, dose-related information was calculated for different head and body clinical protocols. METHODS: The PENELOPE/penEasy package has been used to model the single axial and helical procedures and the radiation transport of photons and electrons in the phantoms. The bowtie filters, heel effect, focal-spot angle, and fan-beam geometry were incorporated. Head and body protocols with different pitch values were modeled for x-ray spectra corresponding to 80, 100, 120, and 140 kV. The analytical formulation for the single dose distributions and experimental measurements of single and accumulated dose distributions were employed to validate the MC results. The experimental dose distributions were measured with OSLDs and a thimble ion chamber inserted into PMMA phantoms. Also, the experimental values of the C T D I 100 along the center and peripheral axes of the CTDI phantom served to calibrate the simulated single and accumulated dose distributions. RESULTS: The match of the simulated dose distributions with the reference data supports the correct modeling of the heel effect and the radiation transport in the phantom material reflected in the tails of the dose distributions. The validation of the x-ray source model was done comparing the CTDI ratios between simulated, measured and CTDosimetry data. The average difference of these ratios for head and body protocols between the simulated and measured data was in the range of 13-17% and between simulated and CTDosimetry data varied 10-13%. The distributions of simulated doses and those measured with the thimble ion chamber are compatible within 3%. In this study, it was demonstrated that the efficiencies of the C T D I 100 measurements in head phantoms with nT = 20 mm and 120 kV are 80.6% and 87.8% at central and peripheral axes, respectively. In the body phantoms with n T = 40 mm and 120 kV, the efficiencies are 56.5% and 86.2% at central and peripheral axes, respectively. In general terms, the clinical parameters such as pitch, beam intensity, and voltage affect the Deq values with the increase of the pitch decreasing the Deq and the beam intensity and the voltage increasing its value. The H(L) function does not change with the pitch values, but depends on the phantom axis (central or peripheral). CONCLUSIONS: The computation of the pitch-equilibrium dose product, D ̂ eq , evidenced the limitations of the C T D I 100 method to determine the dose delivered by a CT scanner. Therefore, quantities derived from the C T D I 100 propagate this limitation. The developed MC model shows excellent compatibility with both measurements and literature quantities defined by AAPM Reports 111 and 200. These results demonstrate the robustness and versatility of the proposed modeling method.


Assuntos
Benchmarking , Radiometria , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação , Tomografia Computadorizada por Raios X
10.
Anticancer Res ; 41(10): 4929-4936, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593440

RESUMO

BACKGROUND/AIM: A new set of LQB-nitrones and analogues was synthesized to evaluate anticancer activity based on the substitution of the terpenyl moiety of the antileukemic compound LQB-278 by the conformationally restricted cinnamyl ether. MATERIALS AND METHODS: A structure-activity relationship study was performed in vitro on Jurkat cells to screen the antileukemic activity of LQB-nitrones and analogues and elucidate the mechanisms of action of the most active derivatives. RESULTS: The cynamyl ramification and its ortho position aldehyde substitution improved the antileukemic activity. Three compounds showed an in vitro antiproliferative action, but only 5b induced apoptosis. Analysis of the molecular mechanisms showed increased expression of the cell cycle inhibitor p21CIP1/WAF1/Sdi1, caspase 3, Fas receptor, and Bax/Bcl-2 ratio. CONCLUSION: The cinnamyl derivative 5b (LQB-461) presented higher antileukemic effects than the prototype terpenyl nitrone, inducing Jurkat cell death by activating both extrinsic and intrinsic pathways of apoptosis. Therefore, this compound is a new promising candidate drug against leukemia.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Iminas/química , Leucemia/tratamento farmacológico , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/farmacologia , Apoptose , Proliferação de Células , Humanos , Leucemia/patologia , Células Tumorais Cultivadas
11.
ACS Med Chem Lett ; 12(9): 1405-1412, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34531949

RESUMO

5-Nitro-furan nitrones (1) and 5-nitro-thiophene nitrones (2) were synthesized in one step. Compounds 1a-c had the most potent leishmanicidal activity against intracellular amastigote forms of Leishmania amazonensis and L. infantum (from 0.019 to 2.76 µM), with excellent selectivity (from 39 to 5673). The comparison of the leishmanicidal activity in promastigotes of wild type L. donovani with those overexpressing nitroreductases NRT1 or NRT2 shows that 1a,b are activated by both, which could slow the development of resistance. Their redox potential (E redox) obtained by cyclic voltammetry (-0.67 and -0.62 V) shows that the reduction of the nitro group is modulated by the nitrone group. Oral administration of 1b to mice infected by L. infantum reduced the parasite load on the spleen by 76.6 and 95.0% with doses of 50 and 100 mg/kg, respectively, administered twice a day, for 5 days. In the liver, the parasite load suppression was above 75% with either treatment.

12.
Beilstein J Org Chem ; 17: 1096-1140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093879

RESUMO

The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.

13.
Int J Oncol ; 58(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33786613

RESUMO

Acute myeloid leukemia (AML) is a complex hematological disorder characterized by blockage of differentiation and high proliferation rates of myeloid progenitors. Anthracycline and cytarabine­based therapy has remained the standard treatment for AML over the last four decades. Although this treatment strategy has increased survival rates, patients often develop resistance to these drugs. Despite efforts to understand the mechanisms underlying cytarabine resistance, there have been few advances in the field. The present study developed an in vitro AML cell line model resistant to cytarabine (HL­60R), and identified chromosomal aberrations by karyotype evaluation and potential molecular mechanisms underlying chemoresistance. Cytarabine decreased cell viability, as determined by MTT assay, and induced cell death and cell cycle arrest in the parental HL­60 cell line, as revealed by Annexin V/propidium iodide (PI) staining and PI DNA incorporation, respectively, whereas no change was observed in the HL­60R cell line. In addition, the HL­60R cell line exhibited a higher tumorigenic capacity in vivo compared with the parental cell line. Notably, no reduction in tumor volume was detected in mice treated with cytarabine and inoculated with HL­60R cells. In addition, western blotting revealed that the protein expression levels of Bcl­2, X­linked inhibitor of apoptosis protein (XIAP) and c­Myc were upregulated in HL­60R cells compared with those in HL­60 cells, along with predominant nuclear localization of the p50 and p65 subunits of NF­κB in HL­60R cells. Furthermore, the antitumor effect of LQB­118 pterocarpanquinone was investigated; this compound induced apoptosis, a reduction in cell viability and a decrease in XIAP expression in cytarabine­resistant cells. Taken together, these data indicated that acquired cytarabine resistance in AML was a multifactorial process, involving chromosomal aberrations, and differential expression of apoptosis and cell proliferation signaling pathways. Furthermore, LQB­118 could be a potential alternative therapeutic approach to treat cytarabine­resistant leukemia cells.


Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/tratamento farmacológico , Naftoquinonas/farmacologia , Pterocarpanos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Citarabina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Camundongos , Naftoquinonas/uso terapêutico , Pterocarpanos/uso terapêutico , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Bioorg Chem ; 110: 104790, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33743223

RESUMO

α-aryl-α-tetralones and α-fluoro-α-aryl-α-tetralones derivatives were synthesized by palladium catalyzed α-arylation reaction of α-tetralones and α-fluoro-α-tetralones, with bromoarenes in moderate to good yields. These compounds were evaluated for their in vitro anti-proliferative effects against human breast cancer and leukemia cell lines with diverse profiles of drug resistance. The most promising compounds, 3b, 3c, 8a and 8c, were effective on both neoplastic models. 3b and 8a induced higher toxicity on multidrug resistant cells and were able to avoid efflux by ABCB1 and ABCC1 transporters. Theoretical calculations of the physicochemical descriptors to predict ADMETox properties were favorable concerning Lipinski's rule of five, results that reflected on the low effects on non-tumor cells. Therefore, these compounds showed great potential for development of pharmaceutical agents against therapy refractory cancers.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Software , Tetralonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Tetralonas/síntese química , Tetralonas/química
15.
J Org Chem ; 86(6): 4849-4858, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33683900

RESUMO

3-Arylidenechroman-4-ones and 2-arylidene-1-tetralones are hydrogenated to cis-benzylic alcohols in dr's and er's up to 99:1 via a C═C and C═O one-pot reduction in the presence of 2-5 mol % Noyori-Ikariya-type RuII chiral complexes and HCO2Na as a hydrogen source under asymmetric transfer hydrogenation-dynamic kinetic resolution (ATH-DKR) conditions. The oxidation of theses substrates resulted in the enantioselective synthesis of the natural homoisoflavanone dihydrobonducellin and its carba-analogues.


Assuntos
Tetralonas , Catálise , Hidrogenação , Cinética , Estereoisomerismo
16.
Bioorg Chem ; 107: 104584, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33453646

RESUMO

Natural pterocarpans and synthetic 5-carba-pterocarpans are isosteres in which the oxygen atom at position 5 in the pyran-ring of pterocarpans is replaced by a methylene group. These 5-carba-analogues were obtained in good yields through the palladium-catalyzed oxyarylation of alcoxy-1,2-dihydronaphthalens with o-iodophenols in PEG-400. They were evaluated on human cancer cell lineages derived respectively from prostate tumor (PC3, IC50 = 11.84 µmol L-1, SI > 12)) and acute myeloid leukemia (HL-60, IC50 = 8.81 µmol L-1, SI > 16), highly incident cancer types presenting resistance against traditional chemotherapeutics. Compound 6c (LQB-492) was the most potent (IC50 = 3.85 µmol L-1, SI > 37) in SF-295 cell lineage (glioblastoma). Such findings suggest that 5-carba-pterocarpan can potentially be new hit compounds for further development of novel antiproliferative agents.


Assuntos
Antineoplásicos/farmacologia , Pterocarpanos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Pterocarpanos/síntese química , Pterocarpanos/química , Relação Estrutura-Atividade
17.
Comput Biol Chem ; 87: 107293, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32559640

RESUMO

Currently Alzheimer's disease (AD) is a devastating neurological disorder that mainly affects the elderly. The treatment of AD has as main objective to increase the levels of ACh in the synaptic cleft by inhibiting the cholinesterase enzymes, which are responsible for the degradation of ACh. Twenty one synthesized coumarins and neoflavanones (4-arylcoumarins) and theoretical studies were used to select the most promising ligands for in vitro experimental studies by Nuclear Magnetic Resonance. The eight compounds selected for the experimental study only 12b (effectiveness 68.54 ±â€¯3.22%) was promising AChE inhibitor. This compound (12b) presents substituents at positions 4, 5, 6, 7 and 8 in a coumarin nucleus, being the most significant characteristic in comparison to the other studied compounds. These results can be used for the design and synthesis of other possible derivatives with inhibitory potential of AChE.

18.
Oncol Rep ; 43(1): 346-357, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746438

RESUMO

Glioblastoma (GBM) is the most frequent malignant brain tumor. It represents the most aggressive astrocytoma with an overall survival of 14 months. Despite improvements in surgery techniques, radio­ and chemotherapy, most patients present treatment resistance, recurrence and disease progression. Therefore, development of effective alternative therapies is essential to overcome treatment failure. The purpose of the study was to evaluate the antitumoral activity of the synthetic compound LQB­118, in vitro. Monolayer and three­dimensional (3D) cell culture systems of human­derived GBM cell lines were used to evaluate the effect of LQB­118 on cell viability, cell death and migration. LQB­118 reduced cell viability as determined by MTT and trypan blue exclusion assays and promoted apoptosis in monolayer cell lines with an intrinsic temozolomide (TMZ)­resistance profile. In 3D culture models, LQB­118 reduced cell viability as evaluated by APH assay and inhibited cell migration while the TMZ resistance profile was maintained. Moreover, LQB­118 reduced p38 and AKT expression and phosphorylation, whereas it reduced only the phosphorylated ERK1/2 form. LQB­118 reduced p38 and NRF2 expression, an axis that is associated with TMZ resistance, revealing a mechanism to overcome resistance. LQB­118 also demonstrated an additional effect when combined with ionizing radiation and cisplatin. In conclusion, the present data demonstrated that LQB­118 maintained its effectiveness in a 3D cell conformation, which shares more similarities with the tumor mass. LQB­118 is a promising agent for GBM treatment as monotherapy and associated with radiotherapy or cisplatin. Its effect is associated with inhibition of GBM­related survival signaling pathways.


Assuntos
Neoplasias Encefálicas/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioblastoma/metabolismo , Naftoquinonas/farmacologia , Proteínas Quinases/metabolismo , Pterocarpanos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Glioblastoma/tratamento farmacológico , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Temozolomida , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
J Org Chem ; 84(17): 10593-10605, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31348647

RESUMO

Catalytic enantioselective 1,3-dipolar cycloaddition between imino esters and electrophilic alkenes, employing chiral metal complexes derived from copper(I) and silver(I) salts and (S)-DM- or (S)-DTBM-Segphos as ligands produces diastereodivergently exo- or endo-cycloadducts, respectively. The effect of the functional group of the dipolarophile and the fine tuning of the catalyst plays an important role in promoting reverse diastereoselectivities. The origins of experimentally observed enantioselectivity and diastereoselectivity data, as well as the origin of the observed switched endo/exo ratios, are also explained by means of density functional theory calculations.

20.
Phys Med Biol ; 64(10): 105010, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-30959490

RESUMO

Mean glandular dose is the quantity used for dosimetry in mammography and depends on breast-related characteristics, such as thickness and density, and on the x-ray spectrum used for breast imaging. This work aims to present an experimentally-based method to derive polyenergetic normalized glandular dose coefficients (DgNp) from the spectral difference between x-ray spectra incident and transmitted through breast phantoms with glandular/adipose proportions of 30/70 and 50/50 and thicknesses up to 4.5 cm. The spectra were produced by a Mammomat 3000 Nova system using radiographic techniques commonly applied for imaging compressed breast thickness lower than 6 cm (Mo/Mo, Mo/Rh and W/Rh spectra at 26 and 28 kVp). DgNp coefficients were compared with values estimated using Boones' method and data from breast images (DICOM Organ Dose and VolparaDose calculations). The DgNp were also evaluated in layers into the phantoms (depth-DgNp) using both x-ray spectra and thermoluminescent dosimeters (TLD-100). Maximum differences between DgNp from the method presented in this study and results using Boone's method was 11%, with larger differences for Mo/Rh spectra in relation to the Mo/Mo. The DgNp maximum differences to the coefficients obtained using patient images were 8.0%, for the DgN calculated using Volpara and 6.4% for the DgN from DICOM Organ Dose, for a 4.5 cm breast phantom with 30% glandularity. The DgNp estimated from the depth-DgNp distributions differ up to 5.2% to the coefficients obtained using the pair incident-transmitted spectra to calculate the DgNp directly in the whole phantom. The depth-DgNp distributions estimated with TLDs were consistent with the results observed using the experimental spectra, with maximum difference of 3.9%. In conclusion, polyenergetic x-ray spectrometry proved to be an applicable tool for research in dosimetry in mammography allowing spectral characterization. This approach can also be useful for investigation of the influence of x-ray spectra on glandular dose.


Assuntos
Algoritmos , Mama/efeitos da radiação , Mamografia/métodos , Método de Monte Carlo , Imagens de Fantasmas , Radiometria/métodos , Mama/diagnóstico por imagem , Feminino , Humanos , Doses de Radiação , Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA