RESUMO
Inhibition of α-glucosidase and α-amylase is an important target for treatment of type 2 diabetes. In this work, a novel series of pyrano[2,3-b]chromene derivatives 5a-m was designed based on potent α-glucosidase and α-amylase inhibitors and synthesized by simple chemical reactions. These compounds were evaluated against the latter enzymes. Most of the title compounds exhibited high inhibitory activity against α-glucosidase and α-amylase in comparison to standard inhibitor (acarbose). Representatively, the most potent compound, 4-methoxy derivative 5d, was 30.4 fold more potent than acarbose against α-glucosidase and 6.1 fold more potent than this drug against α-amylase. In silico molecular modeling demonstrated that compound 5d attached to the active sites of α-glucosidase and α-amylase with a favorable binding energies and established interactions with important amino acids. Dynamics of compound 5d also showed that this compound formed a stable complex with the α-glucosidase active site. In silicodrug-likeness as well as ADMET prediction of this compound was also performed and satisfactory results were obtained.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores de Glicosídeo Hidrolases , Humanos , Inibidores de Glicosídeo Hidrolases/química , Acarbose , Diabetes Mellitus Tipo 2/tratamento farmacológico , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Cromonas/farmacologia , Cromonas/química , alfa-Amilases , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Adolescent obesity is considered as a major health concern worldwide which is closely linked to the quality of diet. The purpose of the present study was to assess the carbohydrate quality and quantity in relation to odds of overweight and obesity in adolescents. METHODS: This case-control study with a 1:1 ratio was conducted on 406 adolescents (14 to 18 years old) matched for age and gender. Participants were selected by multistage cluster random sampling method from March to October 2019 in Shiraz, Iran. Dietary intakes of the study population were assessed by a validated semi-quantitative food frequency questionnaire. Also anthropometric indices were measured using standard methods and demographic information was recorded via face to face interview. The relation between low carbohydrate diet score (LCDS) and carbohydrate quality index (CQI), and odds of obesity was evaluated by multiple Logistic regression. RESULTS: After adjusting the role of potential confounders, the participants in the third tertiles of LCDS (OR = 0.443, 95% CI = (0.260 to 0.755)) and CQI (OR = 0.005, 95% CI = (0.001 to 0.025)) had less odds of being overweight and obese compared to the first tertile. CONCLUSION: The present study found an inverse relationship between dietary quantity and quality of carbohydrate intake and the odds of overweight and obesity in a sample of Iranian adolescents.
Assuntos
Carboidratos da Dieta , Obesidade Infantil , Humanos , Adolescente , Irã (Geográfico)/epidemiologia , Sobrepeso/epidemiologia , Estudos de Casos e Controles , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia , Dieta , Dieta com Restrição de Carboidratos , Índice de Massa CorporalRESUMO
Herein, a novel series of 4,5-diphenyl-imidazol-α-aminophosphonate hybrids 4a-m was designed, synthesized, and evaluated as new anti-diabetic agents. These compounds were evaluated against two important target enzymes in the diabetes treatment: α-glucosidase and α-amylase. These new compounds were synthesized in three steps and characterized by different spectroscopic techniques. The in vitro evaluations demonstrated that all the synthesized compounds 4a-m were more potent that standard inhibitor acarbose against studied enzymes. Among these compound, the most potent compound against both studied enzymes was 3-bromo derivative 4l. The latter compound with IC50 = 5.96 nM was 18-times more potent than acarbose (IC50 = 106.63 nM) against α-glucosidase. Moreover, compound 4l with IC50 = 1.62 nM was 27-times more potent than acarbose (IC50 = 44.16 nM) against α-amylase. Molecular docking analysis revealed that this compound well accommodated in the binding site of α-glucosidase and α-amylase enzymes with notably more favorable binding energy as compared to acarbose.
Assuntos
Acarbose , Inibidores de Glicosídeo Hidrolases , Acarbose/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , Hipoglicemiantes/química , alfa-Amilases/metabolismo , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
Although antibiotics are among the most commonly used treatments of acne, there are refractory cases, or they can cause some complications. Recently, leukotriene B4 has been found to play a major role in inflammatory acne lesions. This double blind, randomized clinical trial was conducted on 108 patients with acne who needed systemic therapy and referred to dermatology clinics affiliated to Shiraz University of Medical Sciences. One group (53 patients) received 100 mg doxycycline daily plus placebo and the other group (55 patients) received 100 mg daily doxycycline plus 10 mg daily montelukast. Both groups also received topical benzoyl peroxide 5% every other night. The study period was 3 months and the patients were investigated by lesion count, investigator global assessment (IGA), global acne grading system (GAGS), and Cardiff acne disability index (CADI) scoring systems. Total lesion count, inflammatory lesion count, and non-inflammatory lesion count as well as IGA and GAGS decreased in both treatment groups. At the end of the study, however, the inflammatory lesion count and IGA score reduced more significantly in the montelukast group (p = 0.018 and 0.045, respectively). In addition, the two groups were significantly different with regard to the percentage of decrease in the total lesion count, inflammatory lesions, and IGA (p = 0.033, 0.003, and 0.044, respectively). Thus, montelukast can be used as an adjuvant therapy besides other treatments of acne, especially for inflammatory lesions.
Assuntos
Acne Vulgar , Fármacos Dermatológicos , Acetatos , Acne Vulgar/patologia , Antibacterianos , Peróxido de Benzoíla , Ciclopropanos , Método Duplo-Cego , Doxiciclina/uso terapêutico , Géis/uso terapêutico , Humanos , Imunoglobulina A/uso terapêutico , Leucotrieno B4/uso terapêutico , Quinolinas , Sulfetos , Resultado do TratamentoRESUMO
Discovery of novel anticancer agents is of crucial importance to expand the therapeutic options for cancer patients. In this study, a series of 49 5-oxo-hexahydroquinoline and 5-oxo-tetrahydrocyclopentapyridine analogs, containing different pyridine alkyl carboxylates at C3 and various aliphatic, aromatic, and heteroaromatic substitutions at the C4 position of the central core, were synthesized. The target compounds were tested for antiproliferative effect against three human cancer cell lines including MOLT-4 (acute lymphoblastic leukemia), K562 (chronic myelogenous leukemia), and MCF-7 (breast adenocarcinoma) by MTT assay, and the effect of the most potent derivatives on cell cycle was evaluated by RNase/propidium iodide (PI) flow cytometric assay. Generally, 5-oxo-hexahydroquinoline derivatives (E series) possessed superior antiproliferative activities compared to their 5-oxo-tetrahydrocyclopentapyridine counterparts (F series). 5-Oxo-hexahydroquinoline compounds bearing 2-pyridyl propyl carboxylate (group D) and 3-pyridyl propyl carboxylate (group E) were better antiproliferative agents than those bearing other pyridyl alkyl carboxylates. Five best compounds with IC50 values in the range of 9.5-22.9 µM against MOLT-4 cells were selected for cell-cycle analysis, which revealed that derivatives D5, E3, and E5 with 2,3-dichlorophenyl, 3-nitrophenyl, and 2-nitrophenyl substitutions at C4 position, respectively, may induce apoptosis in MOLT-4 cells. Molecular docking analysis, which was employed to make some predictions on the interaction of the most active derivatives with the binding site of Bcl-2 and Bcl-xL proteins, suggested that the compounds may be well accommodated within the binding sites of these anti-apoptotic proteins via hydrogen-bonding and hydrophobic interactions. The findings of this study present 5-oxo-hexahydroquinoline derivatives as antiproliferative agents with potential apoptosis-inducing ability in cancer cells.
Assuntos
Antineoplásicos , Neoplasias , Quinolinas , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Background and Aims: Inflammation is strongly associated with the severity and mortality rate of SARS-CoV-2 disease (COVID-19). Dietary factors have a crucial role in preventing chronic and systemic inflammation. This study aimed to evaluate the association between energy-adjusted dietary inflammatory index (E-DII) scores and body composition parameters in COVID-19-infected patients compared to noninfected controls. Methods: A total of 133 COVID-19-infected patients and 322 noninfected controls were selected and enrolled from the Cohort Study of Employees of Shiraz University of Medical Sciences. E-DII score was calculated based on a validated food frequency questionnaire (FFQ) and body composition was measured using In-Body 770 equipment. Logistic regression models were utilized to estimate the odds ratio (OR). Results: In the control group, the mean E-DII score was significantly lower than the case group (-2.05 vs. -0.30, P ≤ 0.001), indicating that the diet of COVID-19-infected subjects was more proinflammatory than the controls. For every 1 unit increase in E-DII score, the odds of infection with COVID-19 was nearly triple (OR: 2.86, CI: 2.30, 3.35, P ≤ 0.001). Moreover, for each unit increase in body mass index (BMI), the odds of infection to COVID-19 increased by 7% (OR: 1.07, CI: 1.01, 1.13, P = 0.02). No significant difference was observed for other anthropometric parameters. Conclusion: The findings revealed that obese people and those consuming a more proinflammatory diet were more susceptible to coronavirus infection. Therefore, maintaining ideal body weight and consuming a more anti-inflammatory diet can decrease the probability of COVID-19 infection.
Assuntos
COVID-19 , Composição Corporal , COVID-19/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Dieta , Humanos , Inflamação/complicações , Irã (Geográfico)/epidemiologia , Fatores de Risco , SARS-CoV-2RESUMO
A series of ethyl 2-amino-4H-benzo[h]chromene-3-carboxylate derivatives, having phenyl ring with diverse substituents at C4 position of 4H-benzochromene nucleus, were synthesized via one-pot three-component reaction between various aromatic aldehydes, α-naphthol, and ethyl cyanoacetate. The synthesized compounds were screened for their antityrosinase activity. Compound 4i, bearing 4-dimethylamino substitution on C4-phenyl ring, was the most potent tyrosinase inhibitor (IC50 = 34.12 µM). The inhibition kinetic analysis of 4i indicated that the compound was a competitive tyrosinase inhibitor. Compounds 4a, 4g, 4i and 4j were the effective radical scavengers with EC50s in the range of 0.144-0.943 mM. According to the in silico drug-like and ADME predictions, 4i can be considered as a suitable candidate. Molecular docking results confirmed that the derivative was well accommodated within the mushroom tyrosinase binding site. Therefore, 4i can be introduced as a novel tyrosinase inhibitor that might be a promising lead in medicine, cosmetics, and food industry.
Assuntos
Monofenol Mono-OxigenaseRESUMO
Lichen planus is considered a chronic inflammatory disease which affects different sites, such as the skin, mucous membranes, hair, and nails. Based on the evidence, a complex cytokine network plays a crucial role in lichen planus pathogenesis. The study was aimed at assessing the serum IL-23 levels in the patients with cutaneous and oral lichen planus compared to healthy controls. Method. The study included 30 cutaneous lichen planus patients, 20 oral lichen planus patients, and 33 control subjects. Five milliliters of peripheral blood was obtained from each patient, and the serum was separated. IL-23 levels were determined using the ELISA kit, and the data were analyzed using the Mann-Whitney test. Results. IL-23 levels in the patient serum with oral lichen planus (P value ≤ 0.001) were significantly higher than in controls. Furthermore, there were significant differences in IL-23 serum levels in the patients with cutaneous lichen planus compared to the healthy controls (P value ≤ 0.001). Moreover, IL-23 serum levels were statistically different between patients with cutaneous lichen planus and patients with oral lichen planus (P value ≤ 0.001). Based on the mean concentration of interleukin-23, IL-23 levels were higher in the patients with oral lichen planus than in the patients with cutaneous lichen planus. Conclusions. Elevated serum IL-23 levels in the patients with oral lichen planus may indicate that IL-23 plays a crucial role in the pathogenesis of oral lichen planus. However, more research is needed with a larger sample size.
Assuntos
Subunidade p19 da Interleucina-23/sangue , Líquen Plano Bucal , Líquen Plano , Humanos , Interleucina-23 , Líquen Plano/patologia , Líquen Plano Bucal/patologia , Pele/patologiaRESUMO
INTRODUCTION: Vitiligo is caused by partial or complete destruction of melanocytes in the affected skin area and influences the patient's quality of life. Besides physical involvement, vitiligo patients experience a high level of stress. Depression and Anxiety are common psychiatric disorders in vitiligo patients. AIM: This study, as the first study, evaluates hopelessness, anxiety, depression and general health of vitiligo patients in comparison with normal controls in an Iranian population. METHOD: Hundred patients with vitiligo and hundred healthy controls were examined. General health, depression, hopelessness and anxiety were evaluated based on general health questionnaire. Anxiety, depression and hopelessness levels were analyzed using Chi-Square, and the mean value of general health was evaluated through t-test. RESULTS: The results showed that anxiety and hopelessness levels were significantly higher in vitiligo patients than those who are in healthy controls. This significant difference refers to high levels of anxiety and hopelessness among women with vitiligo. It was also found that the single patients were more anxious, hopeless and depressive, while the married patients were only more anxious and hopeless than those who are in the control group, respectively. General health of patients was significantly worse than in healthy controls. The low level of general health in patients was related to poorer level of general health among women with vitiligo. CONCLUSION: It seems that women with vitiligo are more mentally stressed than men with vitiligo. Both singles and married vitiligo patients suffer from anxiety and hopelessness.
Assuntos
Qualidade de Vida/psicologia , Vitiligo/psicologia , Adolescente , Adulto , Distribuição por Idade , Ansiedade/complicações , Ansiedade/psicologia , Estudos de Casos e Controles , Depressão/complicações , Depressão/psicologia , Feminino , Esperança , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Vitiligo/complicaçõesRESUMO
In this study, benzyl-1,2,3-triazole-linked 5-benzylidene (thio)barbiturate derivatives 7a-d and 8a-h were designed as potential tyrosinase inhibitors and free-radical scavengers. The twelve derivatives were synthesized via the [3+2] cycloaddition reaction of the corresponding benzyl azide as a dipole and the corresponding alkyne as a dipolarophile in the presence of copper(I) species, generated in situ from copper(II)/ascorbate. The thiobarbiturate derivative 8h and the barbiturate derivative 8b bearing 4-fluoro and 4-bromo groups on the benzyl-triazole moiety were found to be the most potent tyrosinase inhibitors with IC50 values of 24.6 ± 0.9 and 26.8 ± 0.8 µM, respectively. Almost all the compounds showed a good radical scavenging activity with EC50 values in the range of 29.9-324.9 µM. Derivatives 7a, 8f, and 8h were the most potent free-radical scavengers with EC50 values of 29.9 ± 0.8, 36.8 ± 0.9, and 39.2 ± 1.1 µM, respectively. The kinetic analysis revealed that compound 8h was a mixed-type tyrosinase inhibitor. The molecular docking analysis indicated that 8b and 8h were well accommodated in the active site of the tyrosinase enzyme and possessed the most negative binding energy values of -8.55 and -8.81 kcal/mol, respectively. Moreover, it was found that the two residues, Asn81 and Glu322, played a significant role in forming stable enzyme-inhibitor complexes.
Assuntos
Barbitúricos/farmacologia , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Barbitúricos/química , Inibidores Enzimáticos/química , Sequestradores de Radicais Livres/química , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologiaRESUMO
The explosion of medical imaging data along with the advent of big data analytics has launched an exciting era for clinical research. One factor affecting the ability to aggregate large medical image collections for research is the lack of infrastructure for automated data annotation. Among all imaging modalities, annotation of magnetic resonance (MR) images is particularly challenging due to the non-standard labeling of MR image types. In this work, we aimed to train a deep neural network to annotate MR image sequence type for scans of brain tumor patients. We focused on the four most common MR sequence types within neuroimaging: T1-weighted (T1W), T1-weighted post-gadolinium contrast (T1Gd), T2-weighted (T2W), and T2-weighted fluid-attenuated inversion recovery (FLAIR). Our repository contains images acquired using a variety of pulse sequences, sequence parameters, field strengths, and scanner manufacturers. Image selection was agnostic to patient demographics, diagnosis, and the presence of tumor in the imaging field of view. We used a total of 14,400 two-dimensional images, each visualizing a different part of the brain. Data was split into train, validation, and test sets (9600, 2400, and 2400 images, respectively) and sets consisted of equal-sized groups of image types. Overall, the model reached an accuracy of 99% on the test set. Our results showed excellent performance of deep learning techniques in predicting sequence types for brain tumor MR images. We conclude deep learning models can serve as tools to support clinical research and facilitate efficient database management.
Assuntos
Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Redes Neurais de ComputaçãoRESUMO
Multidrug resistance (MDR) in cancer cells is often associated with overexpression of ATP-binding cassette (ABC) transporters, including P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated protein 1 (MRP1/ABCC1) and breast cancer resistance protein (BCRP/ABCG2). Modulators of these transporters might be helpful in overcoming MDR. Moreover, exploiting collateral sensitivity (CS) could be another approach for efficient treatment of cancer. Twelve novel 5-oxo-hexahydroquinoline derivatives bearing different aromatic substitutions at C4, while having 2-pyridyl alkyl carboxylate substituents at the C3 were synthesized and evaluated for MDR reversal activity by flow cytometric determination of rhodamine 123, calcein and mitoxantrone accumulations in P-gp, MRP1 and BCRP-overexpressing cell lines, respectively. Furthermore, to confirm the P-gp inhibitory activity, the effect of compounds on the reduction of doxorubicin's IC50 of drug-resistant human uterine sarcoma cell line, MES-SA/DX5, was evaluated. Compounds D6, D5 and D3 (bearing 3-chlorophenyl, 2,3-dichlorophenyl and 4-chlorophenyl substituents at C4 position of 5-oxo-hexahydroquinoline core) were the most potent P-gp, MRP1 and BCRP inhibitors, respectively, causing significant MDR reversal at concentrations of 1-10⯵M. Additionally, D4 (containing 3-flourophenyl) was the most effective MRP1-dependent CS inducing agent. Overall, chlorine containing compounds D6, C4 and D3 were capable of significant inhibition of all 3 important efflux pumps in cancer cells. Moreover, D6 also induced CS triggered by reducing glutathione efflux. In conclusion, some of the 5-oxo-hexahydroquinoline derivatives are effective efflux pump inhibitors capable of simultaneously blocking 3 important ABC transporters involved in MDR, and represent promising agents to overcome MDR in cancer cells.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/fisiologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/fisiologia , Proteínas de Neoplasias/fisiologia , Quinolinas/farmacologia , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular , Cricetinae , Doxorrubicina/farmacologia , Glutationa/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismoRESUMO
Tyrosinase enzyme plays a crucial role in melanin biosynthesis and enzymatic browning process of vegetables and fruits. A series of veratric acid derivatives containing benzylidene-hydrazine moieties with different substitutions were synthesized and their inhibitory effect on mushroom tyrosinase and free radical scavenging activity were evaluated. The results indicated that N'-(4-chlorobenzylidene)-3,4-dimethoxybenzohydrazide (D5) and N'-(2,3-dihydroxybenzylidene)-3,4-dimethoxybenzohydrazide (D12) showed the highest tyrosinase inhibitory activity with IC50 values of 19.72⯱â¯1.84 and 20.63⯱â¯0.79⯵M, respectively, that were comparable with the IC50 value of kojic acid (19.08⯱â¯1.21⯵M). D12 was also a potent radical scavenger with EC50 value of 0.0097⯱â¯0.0011â¯mM. The free radical scavenging activity of D12 was comparable with the standard quercetin. The inhibition kinetic analyzed by Lineweaver-Burk plots revealed that compound D5 was a competitive tyrosinase inhibitor. Molecular docking study was carried out for the derivatives demonstrating tyrosinase inhibitory activity. D5 and D12 possessed the most negative estimated free energies of binding in mushroom tyrosinase active site. Therefore, D5 and D12 could be introduced as potent tyrosinase inhibitors that might be promising leads in medicine, cosmetics and food industry.
Assuntos
Inibidores Enzimáticos/química , Sequestradores de Radicais Livres/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Ácido Vanílico/análogos & derivados , Agaricales/enzimologia , Compostos de Benzilideno/química , Sítios de Ligação/efeitos dos fármacos , Domínio Catalítico , Inibidores Enzimáticos/metabolismo , Hidrazinas/química , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/metabolismo , Pironas/química , Pironas/metabolismo , Ácido Vanílico/química , Ácido Vanílico/metabolismoRESUMO
OBJECTIVE: Subtle and gradual changes occur in the brain years before cognitive impairment due to age-related neurodegenerative disorders. The authors examined the utility of hippocampal texture analysis and volumetric features extracted from brain magnetic resonance (MR) data to differentiate between three cognitive groups (cognitively normal individuals, individuals with mild cognitive impairment, and individuals with Alzheimer's disease) and neuropsychological scores on the Clinical Dementia Rating (CDR) scale. METHODS: Data from 173 unique patients with 3-T T1-weighted MR images from the Alzheimer's Disease Neuroimaging Initiative database were analyzed. A variety of texture and volumetric features were extracted from bilateral hippocampal regions and were used to perform binary classification of cognitive groups and CDR scores. The authors used diagonal quadratic discriminant analysis in a leave-one-out cross-validation scheme. Sensitivity, specificity, and area under the receiver operating characteristic curve were used to assess the performance of models. RESULTS: The results show promise for hippocampal texture analysis to distinguish between no impairment and early stages of impairment. Volumetric features were more successful at differentiating between no impairment and advanced stages of impairment. CONCLUSIONS: MR radiomics may be a promising tool to classify various cognitive groups.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Hipocampo/patologia , Processamento de Imagem Assistida por Computador/métodos , Idoso , Doença de Alzheimer/psicologia , Atrofia/patologia , Disfunção Cognitiva/psicologia , Bases de Dados Factuais , Feminino , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Masculino , Testes de Estado Mental e Demência/estatística & dados numéricosRESUMO
A series of 12 novel 1,4-naphthoquinone-1,2,3-triazole hybrids were designed and synthesized through copper-catalyzed click reaction of 2-(prop-2-ynylamino)naphthalene-1,4-dione (3) and different azidomethyl-benzene derivatives. The synthesized compounds were assessed for their anticancer activity against three cancer cell lines (MCF-7, HT-29 and MOLT-4) by MTT assay. The results showed that the majority of the synthesized compounds displayed cytotoxic activity. Derivatives 6f and 6h, bearing 4-trifluoromethyl-benzyl and 4-tert-butyl-benzyl groups, respectively, as well as intermediate 3 demonstrated good cytotoxic potential against all tested cancer cell lines, among which compound 6f showed the highest activity. Flow cytometric analysis revealed that compounds 3, 6f and 6h arrested cell cycle at G0/G1 phase in MCF-7 cells. Therefore, synthesized aminonaphthoquinone-1,2,3-triazole derivatives can be introduced as promising molecules for further development as potential anticancer agents.
Assuntos
Antineoplásicos/farmacologia , Naftoquinonas/farmacologia , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Química Click , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Células MCF-7 , Estrutura Molecular , Naftoquinonas/química , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
5-Oxo-hexahydroquinoline (5-oxo-HHQ) represents a biologically attractive fused heterocyclic core. Various synthetic analogs of 5-oxo-HHQ have been synthesized and assessed for different biological activities. Some derivatives have exhibited myorelaxant, analgesic, anticancer, antibacterial, antifungal, antitubercular, antimalarial, antioxidant, anti-inflammatory, multidrug resistance reversal, anti-Alzheimer, neuroprotective, antidiabetic, antidyslipidemic and antiosteoporotic activities. This review provides a comprehensive report regarding the preparation and pharmacological characterization of 5-oxo-HHQ derivatives that have been reported so far. This information will be beneficial for medicinal chemists in the field of drug discovery to design and develop new and potent therapeutical agents bearing the 5-oxo-HHQ nucleus.
Assuntos
Quinolinas/química , Quinolinas/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Parassimpatolíticos/química , Parassimpatolíticos/farmacologiaRESUMO
OBJECTIVE: To determine whether machine learning can accurately classify human papillomavirus (HPV) status of oropharyngeal squamous cell carcinoma (OPSCC) using computed tomography (CT)-based texture analysis. METHODS: Texture analyses were retrospectively applied to regions of interest from OPSCC primary tumors on contrast-enhanced neck CT, and machine learning was used to create a model that classified HPV status with the highest accuracy. Results were compared against the blinded review of 2 neuroradiologists. RESULTS: The HPV-positive (n = 92) and -negative (n = 15) cohorts were well matched clinically. Neuroradiologist classification accuracies for HPV status (44.9%, 55.1%) were not significantly different (P = 0.13), and there was a lack of agreement between the 2 neuroradiologists (κ = -0.145). The best machine learning model had an accuracy of 75.7%, which was greater than either neuroradiologist (P < 0.001, P = 0.002). CONCLUSIONS: Useful diagnostic information regarding HPV infection can be extracted from the CT appearance of OPSCC beyond what is apparent to the trained human eye.
Assuntos
Carcinoma de Células Escamosas/complicações , Neoplasias Orofaríngeas/complicações , Infecções por Papillomavirus/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Meios de Contraste , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico por imagem , Orofaringe/diagnóstico por imagem , Orofaringe/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Intensificação de Imagem Radiográfica , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
A novel series of benzimidazole-1,2,3-triazole hybrids containing substituted benzyl moieties were designed, synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. The results indicated that 2-(4-{[1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-1H-benzimidazole (6g) and 2-(4-{[1-(4-bromobenzyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-1H-benzimidazole (6h) exhibited effective inhibitory activity with IC50 values of 9.42 and 10.34 µm, respectively, comparable to that of kojic acid as the reference drug (IC50 = 9.28 µm). Kinetic study of compound 6g confirmed mixed-type inhibitory activity towards tyrosinase indicating that it can bind to free enzyme as well as enzyme-substrate complex. Also, molecular docking analysis was performed to determine the binding mode of the most potent compounds (6g and 6h) in the active site of tyrosinase. Consequently, 6g and 6h derivatives might serve as promising candidates in cosmetics, medicine or food industry, and development of such compounds may be of an interest.
Assuntos
Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Triazóis/farmacologia , Agaricales/enzimologia , Relação Dose-Resposta a Droga , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/químicaRESUMO
The development of biocompatible wound dressings containing therapeutic agents to accelerate wound healing is an interesting field of study in biomedical sciences. Polyvinyl alcohol (PVA) nanofibers were loaded with zinc oxide nanoparticles (ZnO NPs) and curcumin (Cur) through electrospinning. The dressings were characterized by SEM and XRD and FTIR. The antioxidant, antibacterial, and cytotoxic activities Cur/ZnO/PVA nano dressing were evaluated using DPPH radical scavenging assay, disc diffusion method, and MTT assay, respectively. Cur/ZnO/PVA nano dressing showed sustained Cur release about 19.7% and 61.1% after 8h and 168h, respectively. Cur/ZnO NPs/PVA mixture had higher antioxidant potential than PVA, ZnO NPs, and Cur. The dressing showed a good antibacterial effect. The in vivo wound healing effect of different types of prepared dressings, including PVA, Cur/PVA, Cur/ZnO/PVA, and ZnO/ PVA nanofibers, was also investigated. PVA dressing containing Cur/ZnO NPs resulted in the highest increase of wound contraction in rats. The assembly of Cur and ZnO NPs on PVA nanofibers could propose as an effective delivery method to improve the wound healing process. The investigated wound dressing could be commercialized and used on a large scale after proper further studies, including clinical trials.
RESUMO
Using a system that incorporates a variety of food items rather than focusing on individual components can aid in assessing the inflammatory effects of a diet on disease outcomes such as chronic kidney disease (CKD). Therefore, we decided to investigate the association between dietary inflammatory index (DII) and the risk of protein-energy wasting (PEW) and sarcopenia in patients with CKD. In this cross-sectional study, 109 patients with CKD were selected from two clinics in Shiraz, Iran. The intake of individuals' diets was recorded using a validated 168-item food frequency questionnaire. Additionally, Asian Working Group for Sarcopenia (AWGS) guidelines were utilized to evaluate muscles' strength, mass, and function. Also, four International Society of Renal Nutrition and Metabolism (ISRNM) criteria (body mass index, intake of protein, albumin, and urine creatinine) were used to diagnose PEW. Logistic regression was used to assess the association between DII and sarcopenia as well as PEW. The results showed that the intake of saturated fatty acids, trans fatty acids, niacin, beta-carotene, and vitamin C was significantly different between lower and higher DII groups. In the univariate model, higher odds of sarcopenia was observed by each unit increase in DII (odds ratio (OR) = 1.379, 95% confidence interval (CI): 1.042-1.824) and age (OR = 1.073, 95% CI: 1.017-1.132). Additionally, in the multivariate model, the association between DII and age with odds of sarcopenia remained significant (DII: OR = 1.379, 95% CI: 1.030-1.846 and age: OR = 1.063, 95% CI: 1.007-1.121). The current study suggests the possible role of pro-inflammatory foods in worsening muscle health, specifically sarcopenia, in CKD patients. Future longitudinal studies may reveal the causative nature of these correlations.