Publications by authors named "Valentina Pau"

4 Publications

  • Page 1 of 1

Naturally occurring Diels-Alder-type adducts from Morus nigra as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B.

Eur J Med Chem 2018 Jan 7;144:277-288. Epub 2017 Dec 7.

Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy; Center for Life Nano [email protected], Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161, Roma, Italy. Electronic address:

Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatases A and B (PtpA and PtpB) have been recognized as potential molecular targets for the development of new therapeutic strategies against tuberculosis (TB). In this context, we have recently reported that the naturally occurring Diels-Alder-type adduct Kuwanol E is an inhibitor of PtpB (K = 1.6 ± 0.1 μM). Here, we describe additional Diels-Alder-type adducts isolated from Morus nigra roots bark that inhibit PtpB at sub-micromolar concentrations. The two most potent compounds, namely Kuwanon G and Kuwanon H, showed K values of 0.39 ± 0.27 and 0.20 ± 0.01 μM, respectively, and interacted with the active site of the enzyme as suggested by kinetics and mass spectrometry studies. Molecular docking coupled with intrinsic fluorescence analysis and isothermal titration calorimetry (ITC) further characterized the interaction of these promising PtpB inhibitors. Notably, in an Mtb survival assay inside macrophages, Kuwanon G showed inhibition of Mtb growth by 61.3%. All these results point to the common Diels-Alder-type adduct scaffold, and highlight its relevance for the development of PtpB inhibitors as candidate therapeutics for TB.
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http://dx.doi.org/10.1016/j.ejmech.2017.11.087DOI Listing
January 2018

Antimycobacterial activity of new N(1)-[1-[1-aryl-3-[4-(1H-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives.

Bioorg Med Chem Lett 2016 07 19;26(14):3287-3290. Epub 2016 May 19.

Department of Life and Enviromental Sciences, Via Porcell 4, University of Cagliari, 09124 Cagliari, Italy.

N(1)-[1-[1-aryl-3-[4-(1H-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives were design, synthesized and tested for their in vitro antimycobacterial activity. The new compounds showed a moderate antimycobacterial activity against the tested strain of Mycobacterium tuberculosis H37Ra and a significant antimycobacterial activity against several mycobacteria other than tuberculosis strains.
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http://dx.doi.org/10.1016/j.bmcl.2016.05.053DOI Listing
July 2016

Discovery of in vitro antitubercular agents through in silico ligand-based approaches.

Eur J Med Chem 2016 Oct 20;121:169-180. Epub 2016 May 20.

Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53019 Siena, Italy; Sbarro Institute for Cancer Research & Molecular Medicine, Center for Biotechnology, College of Science & Technology, Temple University, BioLife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA. Electronic address:

The development of new anti-tubercular agents represents a constant challenge mostly due to the insurgency of resistance to the currently available drugs. In this study, a set of 60 molecules were selected by screening the Asinex and the ZINC collections and an in house library by means of in silico ligand-based approaches. Biological assays in Mycobacterium tuberculosis H37Ra ATCC 25177 strain highlighted (±)-1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(3,4-dichlorophenyl)piperazine-1-carboxylate (5i) and 3-(4-chlorophenyl)-5-(2,4-dimethylpyrimidin-5-yl)-2-methylpyrazolo[1.5-a]pyrimidin-7(4H)-one (42) as the most potent compounds, having a Minimum Inhibitory Concentration (MIC) of 4 and 2 μg/mL respectively. These molecules represent a good starting point for further optimization of effective anti-TB agents.
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http://dx.doi.org/10.1016/j.ejmech.2016.05.032DOI Listing
October 2016

Endodontic infection and endothelial dysfunction are associated with different mechanisms in men and women.

J Endod 2015 May 19;41(5):594-600. Epub 2015 Mar 19.

Department of Medical Sciences, University of Cagliari, Cagliari, Italy.

Introduction: To investigate the potential link between apical periodontitis (AP) and cardiovascular (CV) function, inflammation markers, endothelial flow reserve (EFR), and levels of asymmetrical dimethylarginine (ADMA), the endogenous inhibitor of nitric oxide synthase (NOS), were measured in young adults with AP aged 20-40 years of both sexes.

Methods: Forty men and 41 women (31 ± 5.71 years) free from periodontal disease, CV disease, and traditional CV risk factors were enrolled in the study. Twenty men and 21 women had AP; 40 healthy individuals matched for age, sex, and physical characteristics were also recruited as controls. All subjects underwent dental and complete physical examination, electrocardiography, conventional and tissue Doppler imaging echocardiography, and measurement of EFR. Interleukin (IL)-2, tumor necrosis factor alpha, reactive oxygen species (ROS), and ADMA were also assessed. Data were analyzed using the 2-tailed Student t test, the Pearson t test (or the Spearman t test for nonparametric variables), and multivariate linear regression analysis.

Results: Echocardiography excluded any morphologic and functional cardiac alteration in all the subjects studied. Patients with AP of both sexes showed a significant reduction in EFR (P < .05) and a significant increase in IL-2 (men: P < .01, women: P < .05), whereas ROS were increased significantly only in women (P < .05). ADMA levels were unchanged in women with AP, but they were significantly increased in men (P < .05). A significant direct correlation between ADMA and IL-2 (r = 0.67, P < .001) and an inverse correlation between ADMA and EFR (r = -0.42, P < .05) in men and a significant inverse correlation between ROS and EFR (r = -0.71, P < .01) in female patients were observed.

Conclusions: The presence of chronic inflammation in young adults with AP may cause early endothelial dysfunction documented by the reduced EFR. AP in men may influence the metabolism of NOS, whereas in women it appears to implicate a more direct detrimental mechanism. This difference is sex dependent and may be attributable to the protective action of estrogen in women.
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http://dx.doi.org/10.1016/j.joen.2015.01.037DOI Listing
May 2015
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