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61.
Rubino MT Agamennone M Campestre C Campiglia P Cremasco V Faccio R Laghezza A Loiodice F Maggi D Panza E Rossello A Tortorella P 《ChemMedChem》2011,6(7):1258-1268
A number of matrix metalloproteinases (MMPs), proteins important in the balance of bone remodeling, play a critical role both in cancer metastasis and in bone matrix turnover associated with the presence of cancer cells in bone. Here, we report the synthesis and biological evaluation of a new class of MMP inhibitors characterized by a bisphosphonate function as the zinc binding group. Since the bisphosphonate group is also implicated in osteoclast inhibition and provides a preferential affinity to biological apatite, the new molecules can be regarded as bone-seeking medicinal agents. Docking experiments were performed to clarify the mode of binding of bisphosphonate inhibitors in the active site of MMP-2. The most promising of the studied bisphosphonates showed nanomolar inhibition against MMP-2 and resulted in potent inhibition of osteoclastic bone resorption in vitro. 相似文献
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64.
Rossella Grande Simone Carradori Valentina Puca Irene Vitale Andrea Angeli Alessio Nocentini Alessandro Bonardi Paola Gratteri Paola Lanuti Giuseppina Bologna Pasquale Simeone Clemente Capasso Viviana De Luca Claudiu T. Supuran 《International journal of molecular sciences》2021,22(21)
Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance. 相似文献
65.
Viviana P. Cyras Salvatore Iannace Jos M. Kenny Analía Vzquez 《Polymer Composites》2001,22(1):104-110
Biocomposites were produced using polycaprolactone and starch as matrix, and sisal fibers as reinforcement. The matrix is a biodegradable commercial product called MaterBi‐Z, which is based on a polycaprolactone and starch system. The relationship between processing conditions and properties is reported. An alkaline treatment was performed in order to improve the adhesion and the compatibility of the fiber with the matrix. The effect of the treatment on the tensile properties and morphology was determined. Fiber content enhances the tensile properties of the biodegradable composite. The experimentally observed tensile properties (modulus and tensile strength) of short sisal fiber reinforced MaterBi‐Z matrix composites with different fiber loading are compared with the existing theories of reinforcement. SEM photomicrographs of the fractured composite surfaces are also analyzed. 相似文献
66.
Silvia Romano Carmela Romano Martina Peconi Alessia Fiore Gianmarco Bellucci Emanuele Morena Fernanda Troili Virginia Cipollini Viviana Annibali Simona Giglio Rosella Mechelli Michela Ferraldeschi Liana Veneziano Elide Mantuano Gabriele Sani Andrea Vecchione Renato Umeton Franco Giubilei Marco Salvetti Rosa Maria Corbo Daniela Scarabino Giovanni Ristori 《International journal of molecular sciences》2022,23(20)
Plasma small RNAs have been recently explored as biomarkers in Huntington’s disease (HD). We performed an exploratory study on nine HD patients, eight healthy subjects (HS), and five psychiatric patients (PP; to control for iatrogenic confounder effects) through an Affymetrix-Gene-Chip-miRNA-Array. We validated the results in an independent population of 23 HD, 15 pre-HD, 24 PP, 28 Alzheimer’s disease (AD) patients (to control the disease-specificity) and 22 HS through real-time PCR. The microarray results showed higher levels of U13 small nucleolar RNA (SNORD13) in HD patients than controls (fold change 1.54, p = 0.003 HD vs. HS, and 1.44, p = 0.0026 HD vs. PP). In the validation population, a significant increase emerged with respect to both pre-HD and the control groups (p < 0.0001). SNORD13 correlated with the status of the mutant huntingtin carrier (r = 0.73; p < 0.001) and the disease duration (r = 0.59; p = 0.003). The receiver operating characteristic (ROC) curve analysis showed the high accuracy of SNORD13 in discriminating HD patients from other groups (AUC = 0.963). An interactome and pathway analysis on SNORD13 revealed enrichments for factors relevant to HD pathogenesis. We report the unprecedented finding of a potential disease-specific role of SNORD13 in HD. It seems to peripherally report a ‘tipping point’ in the pathogenic cascade at the neuronal level. 相似文献
67.
Teresa Freire Mercedes Landeira Cecilia Giacomini María Florencia Festari lvaro Pittini Viviana Cardozo Alina Brosque Leticia Monin Valeria da Costa Paula Faral-Tello Carlos Robello Eduardo Osinaga 《International journal of molecular sciences》2022,23(23)
Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential. 相似文献
68.
Alessandro Agnarelli Andrea Lauer Betrn Athanasios Papakyriakou Viviana Vella Mark Samuels Panagiotis Papanastasopoulos Christina Giamas Erika J. Mancini Justin Stebbing John Spencer Chiara Cilibrasi Angeliki Ditsiou Georgios Giamas 《International journal of molecular sciences》2023,24(1)
Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical analyses, we identify a highly selective small molecule LMTK3 inhibitor, namely C36. Biochemical/biophysical and cellular studies revealed that C36 displays a high in vitro selectivity profile and provides notable therapeutic effect when tested in the National Cancer Institute (NCI)-60 cancer cell line panel. We also report the binding affinity between LMTK3 and C36 as demonstrated via microscale thermophoresis (MST). In addition, C36 exhibits a mixed-type inhibition against LMTK3, consistent with the inhibitor overlapping with both the adenosine 5′-triphosphate (ATP)- and substrate-binding sites. Treatment of different breast cancer cell lines with C36 led to decreased proliferation and increased apoptosis, further reinforcing the prospective value of LMTK3 inhibitors for cancer therapy. 相似文献
69.
Azizollah Habibi Yousef Valizadeh Abdolali Alizadeh Hadi Amiri Rudbari Viviana Mollica Nardo 《Journal of Sulfur Chemistry》2014,35(4):362-372
A series of novel ketene dithioacetals has been synthesized by condensation of active methylene compounds with carbon disulfide in the presence of dialkyl acetylenedicarboxylates. This regioselective reaction provides products in good yield by a Michael addition reaction followed by 5-endo-trig intramolecular cyclization. Structures of synthesized compounds have been characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR, and mass spectra. The crystal structure of compound (C 17H 22O 6S 2) has been determined. 相似文献
70.
Mariarosaria De Falco Alessandra Porritiello Federica Rota Viviana Scognamiglio Amina Antonacci Giovanni del Monaco Mariarita De Felice 《International journal of molecular sciences》2022,23(5)
Generation of the 3′ overhang is a critical step during homologous recombination (HR) and replication fork rescue processes. This event is usually performed by a series of DNA nucleases and/or helicases. The nuclease NurA and the ATPase HerA, together with the highly conserved MRE11/RAD50 proteins, play an important role in generating 3′ single-stranded DNA during archaeal HR. Little is known, however, about HerA-NurA function and activation of this fundamental and complicated DNA repair process. Herein, we analyze the functional relationship among NurA, HerA and the single-strand binding protein SSB from Saccharolubus solfataricus. We demonstrate that SSB clearly inhibits NurA endonuclease activity and its exonuclease activities also when in combination with HerA. Moreover, we show that SSB binding to DNA is greatly stimulated by the presence of either NurA or NurA/HerA. In addition, if on the one hand NurA binding is not influenced, on the other hand, HerA binding is reduced when SSB is present in the reaction. In accordance with what has been observed, we have shown that HerA helicase activity is not stimulated by SSB. These data suggest that, in archaea, the DNA end resection process is governed by the strictly combined action of NurA, HerA and SSB. 相似文献