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1.
Biol Trace Elem Res ; 200(1): 31-48, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33635516

RESUMO

Colorectal cancer (CRC) is currently one of the most frequent malignant neoplasms, ranking 3rd in incidence and 2nd in mortality both in the USA and across the world. The pathogenesis of CRC is a complex interaction between genetic susceptibility and environmental factors such as exposure to metals. Therefore, the present study was intended to assess the imbalances in the concentrations of selected essential/toxic elements (Pb, Cr, Fe, Zn, As, Cd, Cu, Se, Ni, and Hg) in the serum of newly diagnosed colorectal carcinoma patients (n = 165) in comparison with counterpart controls (n = 151) by atomic absorption spectrometry after wet-acid digestion method. Serum carcinoembryonic antigen (CEA) of the CRC patients was determined using immunoradiometric method. Body mass index (BMI) which is an established risk factor for CRC was also calculated for patients and healthy controls. Conversely, average Ni (2.721 µg/g), Cd (0.563 µg/g), As (0.539 µg/g), and Pb (1.273 µg/g) levels were significantly elevated in the serum of CRC patients compared to the healthy donors, while the average Se (7.052 µg/g), Fe (15.67 µg/g), Cu (2.033 µg/g), and Zn (8.059 µg/g) concentrations were elevated in controls. The correlation coefficients between the elements in the cancerous patients demonstrated significantly dissimilar communal relationships compared with the healthy subjects. Significant differences in the elemental levels were also showed for CRC types (primary colorectal lymphoma, gastrointestinal stromal tumor, and adenocarcinoma) and CRC stages (stage-I, stage-II, stage-III, and stage-IV) among the patients. Majority of the elements demonstrated perceptible disparities in their levels based on dietary, habitat, gender, and smoking habits of the malignant patients and healthy subjects. Multivariate methods revealed noticeably divergent apportionment among the toxic/essential elements in the cancerous patients than the healthy counterparts. Overall, the study showed significantly divergent distribution and associations of the essential and toxic elemental levels in the serum of the CRC patients in comparison with the healthy donors.


Assuntos
Neoplasias Colorretais , Oligoelementos , Humanos , Metais , Fumar , Espectrofotometria Atômica , Oligoelementos/análise
2.
Bioorg Chem ; 117: 105404, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34749116

RESUMO

Alzheimer's disease (AD) diagnoses are greatly increasing in frequency as the global population ages, highlighting an urgent need for new anti-AD strategies. With the aim to search for human acetylcholinesterase (hAChE) inhibitors from the species of Myrtaceae family, ten acylphloroglucinol trimers (APTs), including eight new APTs, callistemontrimers A-H (1a, 1b, 2a, 2b, 3a, 3b, 4b, and 5b), and two naturally occurring ones (4a and 5a), along with one reported triketone-acylphloroglucinol-monoterpene adduct (6), were obtained and structurally characterized from the hAChE inhibitory acetone extract of Callistemon salignus seeds. The structures and their absolute configurations for new APTs were unequivocally established via the detailed interpretation of extensive spectroscopic data (HRESIMS and NMR), ECD calculations, and single crystal X-ray diffraction, whereas the absolute configurations of known APTs were determined by further chiral separation, and calculated ECD calculations. The results of hAChE inhibitory assay revealed that an enantiomeric mixture of 2a/2b, 2a, and 2b are good hAChE inhibitors with IC50 values of 1.22 ±â€¯0.23, 2.28 ±â€¯0.19, and 4.96 ±â€¯0.39 µM, respectively. Molecular docking was used to uncover the modes of interactions for bioactive compounds with the active site of hAChE. In addition, 2 and 6 displayed moderate neurite outgrowth-promoting effects with differentiation rates of 6.16% and 6.19% at a concentration of 1.0 µM, respectively.

3.
Adv Mater ; : e2104761, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34632640

RESUMO

Elastomeric dielectrics are crucial for reliably governing the carrier densities in semiconducting channels during deformation in soft/stretchable field-effect transistors (FETs). Uncontrolled stacking of polymeric chains renders elastomeric dielectrics poorly insulated at nanoscale thicknesses, thereby thick films are usually required, leading to high voltage or power consumption for on/off operations of FETs. Here, layer-by-layer assembly is exploited to build 15-nm-thick elastomeric nanodielectrics through alternative adsorption of oppositely charged polyurethanes (PUs) for soft and hysteresis-free FETs. After mild thermal annealing to heal pinholes, such PU multilayers offer high areal capacitances of 237 nF cm-2 and low leakage current densities of 3.2 × 10-8 A cm-2 at 2 V. Owing to the intrinsic ductility of the elastomeric PUs, the nanofilms possess excellent dielectric properties at a strain of 5% or a bending radius of 1.5 mm, while the wrinkled counterparts show mechanical stability with negligible changes of leakage currents after repeated stretching to a strain of 50%. Besides, these nanodielectrics are immune to high humidity and conserve their properties when immersed into water, despite their assembly occurs aqueously. Furthermore, the PU dielectrics are implemented in carbon nanotube FETs, demonstrating low-voltage operations (< 1.5 V) and negligible hysteresis without any encapsulations.

4.
Bioorg Chem ; 116: 105303, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34464815

RESUMO

Eucalyptus is a large genus of the Myrtaceae family with high value in various fields of industry. Recently, attention has been focused on the functional properties of Eucalyptus extracts. These extracts have been traditionally used to combat various infectious diseases, and volatile oils are usually considered to play a major role. But the positive effects of non-volatile acylphloroglucinols, a class of specialized metabolites with relatively high content in Eucalyptus, should not be neglected. Herein, non-volatile acylphloroglucinols from leaves of Eucalyptus robusta were evaluated for their abilities to inhibit Zika virus (ZIKV) which is associated with severe neurological damage and complications. The results showed eucalyprobusone G, a new symmetrical acylphloroglucinol dimer, possessed the significant ability to inhibit ZIKV without inducing cytotoxicity. The EC50 values of eucalyprobusone G against the African lineage (MR766) and Asian lineage (SZ-WIV01) of ZIKV were 0.43 ± 0.08 and 10.10 ± 3.84 µM which were 110 times and 5.8 times better than those of the reference compound ribavirin, respectively. Further action mode research showed that eucalyprobusone G impairs the viral binding and RdRp activity of NS5. The results broaden the functional properties of Eucalyptus robusta and indicate acylphloroglucinol dimers could be developed as anti-ZIKV agents.

5.
Chin Med J (Engl) ; 134(14): 1687-1694, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34397595

RESUMO

BACKGROUND: Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established. METHODS: A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set. RESULTS: The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize. CONCLUSIONS: After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Medição de Risco , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X
6.
Phytother Res ; 35(9): 5282-5289, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34314073

RESUMO

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered DNA repair enzyme that can repair topoisomerase 2-mediated DNA damage, resulting in cancer cell resistance. In this study, two compounds, robustadial A and B, were isolated from a fraction of the ethyl acetate extract of Eucalyptus globulus Labill. fruits based on TDP2 inhibition screening. The biological experiments indicated that robustadial A and B have TDP2 inhibitory activity with EC50 values of 17 and 42 µM, respectively, but no tyrosyl-DNA phosphodiesterase 1 inhibition at 100 µM. Robustadial A showed significant synergistic effects with the anticancer drug etoposide in four human cancer cell lines, non-small cell lung cancer cell line (A549), prostate cancer cell line (DU145), breast cancer cell line (MCF-7), colorectal adenocarcinoma cell line (HCT-116), and chicken lymphoma cell line (DT40), and chicken lymphoma cell line complementation with human TDP2 (DT40 hTDP2) with combination index values ranging from 0.21 to 0.74. This work will facilitate future efforts for the development of robustadial A-based TDP2 selective inhibitors.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Eucalyptus , Neoplasias , Inibidores de Fosfodiesterase , Animais , Linhagem Celular Tumoral , Galinhas , Proteínas de Ligação a DNA , Eucalyptus/química , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases
7.
World J Clin Cases ; 9(13): 3170-3176, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33969105

RESUMO

BACKGROUND: Perioperative stroke is a rare but devastating complication. The risk factors for massive cerebral stroke in surgical patients include older age, male sex, prior cerebrovascular disease, hypertension, renal failure, smoking, diabetes mellitus, and atrial fibrillation. CASE SUMMARY: We describe two cases of perioperative massive cerebral stroke following thoracic surgery and one case following bronchoscopy. Neurologic symptoms, including changes in mental status and hemiplegia, occurred within 10 h after surgery in the three patients. All three patients died after the surgery. CONCLUSION: Perioperative massive cerebral stroke may be more likely to occur in thoracic surgical patients if there are pre-existing factors including previous stroke, hypotension, and hypoxemia. Sufficient pain control after surgery and timely neurology consultation and management are helpful for the diagnosis and control of stroke in high-risk patients.

8.
J Phys Chem B ; 125(22): 5683-5693, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34042460

RESUMO

Photophysical properties of five kinds of porphyrins (H2TMPyP, ZnTMPyP, PdTMPyP, H2TPPS, and ZnTPPS) complexed with model DNAs (ctDNA and dGMP) have been investigated using steady-state absorption, circular dichroism (CD), and femtosecond transient absorption spectroscopy. Upon addition of ctDNA (or dGMP), larger hypochromism and red shifts are observed for H2TMPyP and PdTMPyP compared to the other samples. The steady-state measurements have suggested that the binding modes of H2TMPyP-ctDNA and PdTMPyP-ctDNA are partial intercalation and full intercalation, respectively, while ZnTMPyP-ctDNA shows outside groove binding. No significant interaction was observed between both H2TPPS and ZnTPPS with two kinds of DNA. Upon excitation of the porphyrins into the higher excited state S2 (Soret band), the appearance of the transient absorption from ∼500 to ∼620 nm at about 0.05 ps in H2TMPyP-ctDNA, H2TMPyP-dGMP, and PdTMPyP-dGMP indicates the occurrence of the electron transfer (ET) from guanine to H2TMPyP and PdTMPyP. The forward ET are extremely fast (kf ≥ 1.0 × 1013 s-1), and the backward ET rates are ∼5.6 × 1012 and ∼4.0 × 1012 s-1, respectively. The complexation with DNA may lead to the shorter lifetime of the fluorescence of H2TMPyP and PdTMPyP.


Assuntos
Porfirinas , Água , Dicroísmo Circular , DNA , Elétrons
10.
Int J Ophthalmol ; 14(2): 269-276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614457

RESUMO

AIM: To assess the effect of age at diabetes onset and uncontrollable high HbA1c levels on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. METHODS: This was a cross-sectional survey of diabetic patients in Subei district, China. Data covering physical measurements, fasting blood-glucose (FBG), glycosylated hemoglobin (HbA1c), blood lipid, urinary albumin/creatinine ratio (UACR), ocular fundus examination, and diabetes treatment records were collected. An independent sample t-test were used to analyze differences. A Logistic regression analysis was applied to study the independent risk factors of DR. RESULTS: A total of 1282 patients with type 2 DM were enrolled, and 191 cases had DR (14.9%). The age at diabetes onset, education level, alcohol consumption, HbA1c level, UACR level, and hypoglycemic drugs were independent influencing factors for DR. The older the onset of diabetes, the less likely to develop DR (OR: 0.958, 95%CI: 0.942-0.975, P=0.000). Patients were then divided in terms of age at diabetes onset as follows: <50y, 50-59y, 60-69y, and ≥70y. Compared with diabetes onset age <50y, 50-59y (OR: 0.463, 95%CI: 0.306-0.699, P=0.000), 60-69y (OR: 0.329, 95%CI: 0.203-0.535, P=0.000) and ≥70y (OR: 0.232, 95%CI: 0.094-0.577, P=0.002) were at a lower risk of DR. The prevalence of DR was highest in patients with diabetes onset age <50y (29.5%, P<0.05). The HbA1c level (8.67±1.97)% and proportion of insulin injection (52.5%) in patients with diabetes onset <40y were higher than in patients with older diabetes onset age (P<0.05). CONCLUSION: Diabetes onset at an earlier age and uncontrollable high HbA1c level could be independent risk factors for DR.

12.
Inorg Chem ; 60(4): 2234-2245, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33480681

RESUMO

A series of halogenated gallium corroles were synthesized and characterized by UV-vis, HRMS, NMR, and FT-IR. The interaction between these gallium corroles and calf thymus DNA had been investigated by spectroscopic methods. These gallium corroles would interact with CT-DNA via an outside binding mode. The photodynamic antitumor activity in vitro of these gallium corroles toward different cell lines had also been tested. 3-Ga displayed low cytotoxicity to normal cells under both light and dark conditions but high phototoxicity to liver cancer cells HepG2. The vitro experiment results showed that 3-Ga could be efficiently absorbed by tumor cells. After light illumination, it may induce reactive oxygen species (ROS) and cause destruction of the mitochondrial membrane potential, which may finally trigger tumor cell apoptosis. Flow cytometry results showed that HepG2 cells were mainly distributed in the sub-G0 phase, which corresponds to cells with highly fragmented DNA or dead cells generally. This suggests that 3-Ga could lead to tumor cell apoptosis after light illumination.


Assuntos
DNA/química , Gálio/química , Halogenação , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Análise Espectral/métodos , Testes de Toxicidade Aguda
13.
Bioorg Chem ; 107: 104519, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33293058

RESUMO

Chemical investigation of the twigs and leaves of Rhodomyrtus tomentosa led to the isolation and structural identification of a novel polymethylated phloroglucinol meroterpenoid (PPM) featuring a 6/6/6/6 tetracyclic system, rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs) with a rare bis-furan framework, rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two ß-triketone units, rhotomentosone F (7), as well as five known analogues (8-12). Their structures and absolute configurations were unambiguously determined by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. All isolates were evaluated for their anti-inflammatory and acetylcholinesterase (AChE) inhibitory activities. Compound 6 displayed significant AChE inhibitory effect with an IC50 value of 8.68 µM. Further molecular docking studies of 6 revealed that the interactions with AChE residues Ser125, Glu202, and Tyr133 are crucial for AChE inhibitory activity. The current study not only enriches the chemical diversity of phloroglucinols in Myrtaceae species, but also provides potential lead compounds for the further design and development of new AChE inhibitors to treat Alzheimer's disease.


Assuntos
Acetilcolinesterase/metabolismo , Anti-Inflamatórios/farmacologia , Inibidores da Colinesterase/farmacologia , Myrtaceae/química , Floroglucinol/análogos & derivados , Floroglucinol/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Floroglucinol/metabolismo , Folhas de Planta/química , Ligação Proteica , Células RAW 264.7
14.
Eur J Med Chem ; 210: 113068, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33310292

RESUMO

Glioblastoma multiform (GBM) is the highly aggressive brain tumor with poor prognosis. Glioma stem cells (GSCs), small population of cancer cells that exist in GBM tissues, resistant to chemotherapy and radiotherapy and usually driving GBM recurrence, have been developed as effective therapeutic target. Steroidal saponins are one of important resources for anti-tumor agent and may be benefited to selectively clear GSCs. In this report, total of 97 natural steroidal saponins were investigated the relationship among structures/cytotoxicity/selectivity against GSCs, glioma cell lines and human untransformed cells, and revealed that tribulosaponin A was the most potent compound. Further investigation suggested that tribulosaponin A up-regulated the expression of NCF1 and NOX1 to accumulate ROS for triggering apoptosis in GSCs, but not in untransformed cells, and it was further supported by the assay that N-acetyl-l-cysteine (NAC) clearing ROS delayed GSCs apoptosis. Besides, tribulosaponin A damaged GSCs recapturing tumor spheres formation.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Proteína Goosecoid/antagonistas & inibidores , Saponinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Produtos Biológicos/síntese química , Produtos Biológicos/química , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteína Goosecoid/metabolismo , Humanos , Estrutura Molecular , Saponinas/síntese química , Saponinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
15.
Planta Med ; 87(3): 225-235, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33348408

RESUMO

Four new ß-resorcylic acid lactones, including penochrochlactone A (2: ), 4-O-desmethyl-aigialomycin B (4: ), and penochrochlactones C and D (5: and 6: ), two compounds isolated from a natural source for the first time, 5α, 6ß-acetonide-aigialomycin B (1: ) and penochrochlactone B (3: ), together with six known compounds, aigialomycin F (7: ), aigialomycins A, B, and D (8: -10: ), zeaenol (11: ), and oxozeaenol (12: ), were isolated from a mycelial solid culture of the endophytic fungus Penicillium ochrochloron SWUKD4.1850 from the medicinal plant Kadsura angustifolia by sequential purification over silica gel, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and chemical conversions. In addition, all the new compounds were evaluated for their cytotoxic and antibacterial activities in vitro. Penochrochlactone C (5: ) displayed moderate cytotoxicity against the HeLa tumor cell line with an IC50 value of 9.70 µM. In the antibacterial assays, compounds 4:  - 6: exhibited moderate activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa with MIC values between 9.7 and 32.0 µg/mL.


Assuntos
Kadsura , Penicillium , Antibacterianos/farmacologia , Lactonas/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular
16.
Chem Biodivers ; 18(1): e2000772, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33369207

RESUMO

Two new dammarane-type triterpenoid saponins, 3ß-(α-l-arabinopyranosyloxy)-24,25-dihydroxydammar-20-en-12α-yl 6-deoxy-ß-d-glucopyranoside (1) and (24R)-3ß-[(4-O-acetyl-α-l-arabinopyranosyl)oxy]-25-hydroxy-20,24-epoxydammaran-12ß-yl 6-deoxy-ß-d-glucopyranoside (2), and fourteen known triterpenoids were isolated from the 70 % MeOH extract of the leaves of Cyclocarya paliurus. Their structures were established based on analyses of spectroscopic data. All compounds were tested for their inhibitory activities against the 11ß-HSD1 enzyme. Hederagenin (13) exhibited moderate inhibitory effect for mouse 11ß-HSD1 with an IC50 value of 0.16±0.04 µM.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Juglandaceae/química , Compostos Fitoquímicos/química , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Animais , Concentração Inibidora 50 , Juglandaceae/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/metabolismo
17.
Eur J Med Chem ; 208: 112794, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32916313

RESUMO

Three mono-hydroxy corroles 1-3 and their gallium(III) complexes Ga1-3 were synthesized, and their photodynamic antitumour activities towards breast cancer cells were investigated. All corroles showed excellent cytotoxicity against the MDA-MB-231 and 4T1 cell lines upon light irradiation at 625 nm. Ga3 exhibited excellent phototoxicity and selectivity against MDA-MB-231 cells, with an IC50 of 0.06 ± 0.03 µM and a selective index value of 1338.83 (relative to human normal Huvec cells). The performance of Ga3 was even better than that of the clinical photodynamic therapy drug m-THPC. A preliminary mechanistic investigation revealed that corrole 3 and Ga3 were mainly located in the cytoplasm. Upon irradiation, they could generate intracellular reactive oxygen to destroy the mitochondrial membrane potential and arrest the cell cycle at the sub-G1 phase. Flow cytometry revealed that corrole 3 and Ga3 induced cancer cell apoptosis after photodynamic treatment. Corrole 3 and Ga3 displayed negligible cytotoxicity in the dark. These results suggest that corrole 3 and Ga3 are promising candidates for use in the photodynamic therapy of breast cancer.


Assuntos
Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Gálio/química , Humanos , Luz , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Porfirinas/síntese química , Porfirinas/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
18.
Bioorg Chem ; 103: 104127, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745755

RESUMO

Eleven new acylphloroglucinols, including six new formylated phloroglucinol-monoterpene meroterpenoids, eucalyprobusals A-F (1-6), one monomeric acylphloroglucinol, eucalyprobusone B (7), and four dimeric acylphloroglucinols, eucalyprobusones C-F (8-11) were purified from the fruits of Eucalyptus robusta. The establishment of the structures of 1-11 was achieved by a combination of NMR and HRESIMS data analyses, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Compounds 6, 8, and an inseparable mixture of 10 and 11 were found to be potent AChE inhibitors with IC50 values of 3.22 ± 0.36, 3.82 ± 0.22, and 2.55 ± 0.28 µΜ, respectively. Possible interaction sites of 6, 8, 10, and 11 with AChE were investigated by means of molecular docking studies, and the results revealed that AChE residues Asn87, Ser125, Thr83, Tyr133, Tyr124, Tyr337, and Tyr341 played crucial roles in the observed activity of the aforementioned compounds.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Eucalyptus/química , Frutas/química , Floroglucinol/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Floroglucinol/química , Floroglucinol/isolamento & purificação , Relação Estrutura-Atividade
19.
Chem Biodivers ; 17(10): e2000489, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32761773

RESUMO

Rhotomentodiones C-E, three new polymethylated phloroglucinol meroterpenoids with diverse configurations, were isolated from the twigs and leaves of Rhodomyrtus tomentosa. Their structures and absolute configurations were established mainly by means of comprehensive spectroscopic data and electron circular dichroism (ECD) calculation. Among them, Rhotomentodione D (2) exhibited both antibacterial activity with an MIC value of 12.5 µg/mL against Propionibacterium acnes and AChE inhibitory activity with an IC50 value of 22.9 µm.


Assuntos
Antibacterianos/farmacologia , Inibidores da Colinesterase/farmacologia , Myrtaceae/química , Floroglucinol/farmacologia , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Acetilcolinesterase/metabolismo , Antibacterianos/química , Antibacterianos/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Testes de Sensibilidade Microbiana , Floroglucinol/química , Floroglucinol/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Caules de Planta/química , Propionibacterium acnes/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Terpenos/química , Terpenos/isolamento & purificação
20.
Fitoterapia ; 145: 104629, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32428563

RESUMO

Based on a method combining the LC-MS/MS molecular networking strategy with the conventional means of phytochemical research, the chemical constituents and the availability of Paris tengchongensis, a new species found in 2017 from Yunnan Province, were investigated for the first time. The molecular networking showed that this species contained the characteristic steroidal glycosides of the genus Paris by comparison of those of Paris polyphylla var. yunnanensis. Furthermore, the detailed investigation on the 80% EtOH extract of its rhizomes resulted to the isolation of twenty steroidal glycosides including three new spirostane-type saponins, named paristengosides A-C (1-3). Their structures were confirmed by spectroscopic analyses (HRMS and NMR) and chemical methods. The new isolates were evaluated for their cytotoxicities against two human cancer cell lines (HEL and MDA-MB-231), anti-inflammatory effects on a lipopolysaccharide (LPS)-stimulated NO production model in RAW264.7 macrophages, anti-AChE, and antimicrobial activities. The results from the molecular networking and the investigation on the chemical constituents suggested that P. tengchongensis can be used as a potential resource of Rhizoma Paridis.


Assuntos
Melanthiaceae/química , Rizoma/química , Saponinas/farmacologia , Esteroides/farmacologia , Animais , Linhagem Celular Tumoral , China , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Cromatografia Líquida , Humanos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Propionibacterium acnes , Células RAW 264.7 , Saponinas/isolamento & purificação , Esteroides/isolamento & purificação , Espectrometria de Massas em Tandem
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