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31.
Mabrouk Horchani Gerardo Della Sala Alessia Caso Federica DAria Germana Esposito Ilaria Laurenzana Concetta Giancola Valeria Costantino Hichem Ben Jannet Anis Romdhane 《International journal of molecular sciences》2021,22(5)
Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds. 相似文献
32.
Dr. Rita Maria Concetta Di Martino Dr. Giovanni Bottegoni Dr. Francesca Seghetti Dr. Debora Russo Dr. Ilaria Penna Dr. Alessio De Simone Dr. Giuliana Ottonello Dr. Sine Mandrup Bertozzi Dr. Andrea Armirotti Dr. Tiziano Bandiera Prof. Federica Belluti Prof. Andrea Cavalli 《ChemMedChem》2020,15(11):949-954
Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds ( 7 and 10 ) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies. 相似文献
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34.
Fabrizio Cincotta Antonella Verzera Gianluca Tripodi Concetta Condurso 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2018,35(3):512-518
The aim of this research was to develop and validate a headspace-solid phase micro-extraction–gas chromatography–mass spectrometry (HS-SPME–GC–MS) method for the determination of volatile emerging contaminants in fruit. The method showed good precision (RSD ≤ 14%) and satisfactory recoveries (99.1–101.7%) and LOD and LOQ values ranging between 0.011–0.033 μg kg?1 and 0.037–0.098 μg kg?1, respectively. The method was applied to investigate the content of volatile emerging contaminants in two varieties of melon fruit (Cucumis melo L.) cultivated adjoining high-risk areas. Glycol ethers, BHT, BHA and BTEX (benzene, toluene, ethylbenzene and xylene) were determined in melon fruit pulps for the first time, with different sensitivities depending on sample and variety. Although the amount of the volatile contaminants in the melon samples were in the order of µg kg?1, the safety of vegetable crops cultivated near risk areas should be more widely considered. The results showed that this accurate and reproducible method can be useful for routine safety control of fruits and vegetables. 相似文献
35.
Marisa Ziino Concetta Condurso Vincenza Romeo Gianluca Tripodi Antonella Verzera 《Journal of the science of food and agriculture》2009,89(5):774-780
BACKGROUND: Because of the great variability in size, shape, colour, pungency and aroma of Calabrian Capsicum annuum(hot pepper), this study was carried out to furnish producers with information on volatile compounds and capsaicinoid content useful for the genetic improvement of this species. Fully ripened fresh peppers of the most widely cultivated varieties were studied. Capsaicinoid content was determined by reverse phase high‐performance liquid chromatography/diode array detection (RP‐HPLC/DAD). Volatile compounds were determined by headspace solid phase microextraction/gas chromatography/mass spectrometry (HS‐SPME/GC/MS). RESULTS: Sixty‐four volatile compounds were identified, the main classes being alcohols, aldehydes, terpenes and aliphatic branched‐chain hydrocarbons. The ‘Naso di cane’ (C. annuumvar. abbreviatum) variety contained the lowest amount of volatiles, especially alcohols and aldehydes, while the highest levels of capsaicin and dihydrocapsaicin were found in ‘Vulcan’ and ‘Corno di capra’ varieties. CONCLUSION: From statistical evaluation of the data obtained, each variety showed a typical composition of capsaicinoids and volatiles determining the taste and odour of the hot peppers. These results should be useful in the context of research aimed at selecting varieties with the best sensory characteristics. Copyright © 2009 Society of Chemical Industry 相似文献
36.
Amit Shahar Concetta F. Alberti David Clarke David Crundall 《Accident; analysis and prevention》2010,42(6):1577-1584
A typical hazard perception test presents participants with a single-screen view of the road ahead. This study assessed how increasing this field of view would affect hazard perception abilities. Drivers were shown video clips of driving situations containing at least one hazard either on a single screen, or with the addition of side views on two separate but adjacent screens that extended the perceived worldview to approximately 180°. Mirror information was also included to allow information from behind the vehicle to be attended. Participants were instructed to press a button as soon as they saw a hazard. Faster response times were found for hazards that appeared in the centre of the central screen, than in the periphery of the central screen, with hazards that first appeared in the lateral screens responded to slowest. Additionally, responses to the hazards were faster and were more likely to occur in the three-, as compared to the single-screen condition. These results suggest that providing participants with a wider field of view, which includes more environmental cues that are related to the relevant hazardous situation increases their ability to detect hazards, and some limited support to that providing them with a wider view increases this ability even when all hazard-relevant information appear only in the central screen. A number of reasons for the three-screen advantage are discussed. This study suggests that even responses to central hazards may be under-estimated in a typical single-screen hazard perception test, and that improvements can be made for new hazard perception tests, by including visual information from the side and from behind the driver. This new methodology not only allows testing hazard perception skills in a potentially more immersive and realistic environment, but also enables to create hazard perception clips that cannot be realised in a typical single-screen test. 相似文献
37.
Bandura Albert; Caprara Gian Vittorio; Barbaranelli Claudio; Pastorelli Concetta; Regalia Camillo 《Canadian Metallurgical Quarterly》2001,80(1):125
This longitudinal research examined a structural model of the self-regulatory mechanisms governing transgressive conduct. Perceived academic and self-regulatory efficacy concurrently and longitudinally deterred transgressiveness both directly and by fostering prosocialness and adherence to moral self-sanctions for harmful conduct. The impact of perceived social self-efficacy was mediated through prosocialness. Moral disengagement and prosocialness affected transgressiveness through the mediating influence of irascible affectivity and hostile rumination. Ruminative affectivity, in turn, both concurrently and longitudinally affected transgressiveness. Moral disengagement also contributed independently to variance in transgressiveness over time. This pattern of relations was obtained after controlling for prior transgressiveness. The structural model was replicated across gender and provided a better fit to the data than did several alternative models. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
38.
Federico Pallottino Paolo Menesatti Maria Carmela Lanza Maria Concetta Strano Francesca Antonucci Mauro Moresi 《Journal of the science of food and agriculture》2013,93(5):1176-1183
BACKGROUND: The aim of this study was to extract a sorting rule for Tarocco orange fruit from several physicochemical and sensory tests performed on a marketable lot of 399 Tarocco orange fruits. RESULTS: The elastic tension at 5% strain (T5) was found to be linearly correlated (r = 0.65) with the Magness–Taylor (MT) index. Thus T5 was regarded as a non‐destructive parameter quantifying fruit firmness and used to categorise the aforementioned lot in three different firmness classes, high (HF), medium (MF) and low (LF). Only the MT index, fruit rind thickness near the fruit peduncle, lightness coefficient and yellow/blue hue component of the orange flesh, as well as total soluble solid content, confirmed the validity of this discrimination at the significance level of 5%. Sensory professionals recognised the greater compactness (7 ± 2) but lower ease of peeling (4 ± 2) and segment separation (4 ± 2) of the HF oranges with respect to the corresponding sensory attributes of orange fruits grouped in the MF and LF classes. CONCLUSION: To limit the costly rejection of Tarocco orange fruit considered too soft, especially after long‐term shipping, it would be reasonable to select only fruits characterised by a compressive force or tension at 5% strain in the range 23–41 N or 300–540 N m?1 respectively. © 2012 Society of Chemical Industry 相似文献
39.
Francesca Potenza Maria Concetta Cufaro Linda Di Biase Valeria Panella Antonella Di Campli Anna Giulia Ruggieri Beatrice Dufrusine Elena Restelli Laura Pietrangelo Feliciano Protasi Damiana Pieragostino Vincenzo De Laurenzi Luca Federici Roberto Chiesa Michele Sallese 《International journal of molecular sciences》2021,22(22)
Marinesco–Sjogren syndrome (MSS) is a rare multisystem pediatric disorder, caused by loss-of-function mutations in the gene encoding the endoplasmic reticulum cochaperone SIL1. SIL1 acts as a nucleotide exchange factor for BiP, which plays a central role in secretory protein folding. SIL1 mutant cells have reduced BiP-assisted protein folding, cannot fulfil their protein needs, and experience chronic activation of the unfolded protein response (UPR). Maladaptive UPR may explain the cerebellar and skeletal muscle degeneration responsible for the ataxia and muscle weakness typical of MSS. However, the cause of other more variable, clinical manifestations, such as mild to severe mental retardation, hypogonadism, short stature, and skeletal deformities, is less clear. To gain insights into the pathogenic mechanisms and/or adaptive responses to SIL1 loss, we carried out cell biological and proteomic investigations in skin fibroblasts derived from a young patient carrying the SIL1 R111X mutation. Despite fibroblasts not being overtly affected in MSS, we found morphological and biochemical changes indicative of UPR activation and altered cell metabolism. All the cell machineries involved in RNA splicing and translation were strongly downregulated, while protein degradation via lysosome-based structures was boosted, consistent with an attempt of the cell to reduce the workload of the endoplasmic reticulum and dispose of misfolded proteins. Cell metabolism was extensively affected as we observed a reduction in lipid synthesis, an increase in beta oxidation, and an enhancement of the tricarboxylic acid cycle, with upregulation of eight of its enzymes. Finally, the catabolic pathways of various amino acids, including valine, leucine, isoleucine, tryptophan, lysine, aspartate, and phenylalanine, were enhanced, while the biosynthetic pathways of arginine, serine, glycine, and cysteine were reduced. These results indicate that, in addition to UPR activation and increased protein degradation, MSS fibroblasts have profound metabolic alterations, which may help them cope with the absence of SIL1. 相似文献
40.
Francesca DAvanzo Alessandra Zanetti Concetta De Filippis Rosella Tomanin 《International journal of molecular sciences》2021,22(24)
Mucopolysaccharidosis type VI, or Maroteaux–Lamy syndrome, is a rare, autosomal recessive genetic disease, mainly affecting the pediatric age group. The disease is due to pathogenic variants of the ARSB gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB). The enzyme deficit causes a pathological accumulation of the undegraded glycosaminoglycans dermatan-sulphate and chondroitin-sulphate, natural substrates of ASB activity. Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus. Neurocognitive and behavioral abilities, commonly described as maintained, have been actually investigated by few studies. The disease, first described in 1963, has a reported prevalence between 0.36 and 1.3 per 100,000 live births across the continents. With this paper, we wish to contribute an updated overview of the disease from the clinical, diagnostic, and therapeutic sides. The numerous in vitro and in vivo preclinical studies conducted in the last 10–15 years to dissect the disease pathogenesis, the efficacy of the available therapeutic treatment (enzyme replacement therapy), as well as new therapies under study are here described. This review also highlights the need to identify new disease biomarkers, potentially speeding up the diagnostic process and the monitoring of therapeutic efficacy. 相似文献