102,312 research outputs found
Natural Products as Building Blocks for Self-assembled Nanoparticles
No full textOur continuous interest in the field of chemical approaches to target cancer cells moved us to study the preparation of a novel classes of conjugate compounds using anticancer drugs as building blocks. In previous efforts we used squalene tail as self-assembling inducer1 and a disulphide containing linker to secure the release of the drugs after cell internalization.2 Subsequently we demonstrated the possibility to generate hetero and fluorescent nanoparticles by mixing a paclitaxel-squalene conjugate and fluorescein-squalene conjugate.3
In the light of facing the high demanding issue of resistance4 we studied the formation of cyclopamine-paclitaxel containing nanoparticles and we had the way to detect the internalization by confocal microscopy and super-resolution.5 Our efforts are actually focused on: a) new combination of drugs to overcome drug resistance, b) new self-assembling inducers,6 c) new hetero-nanoparticles7 and d) new drug-conjugates deriving by modification of active natural products.
References:
1. G. Fumagalli,D. Passarella et al. Drug Discovery Today 2016, 21, 1321
2. S. Borrelli, A. D. Passarella et al. Eur.J.Med.Chem 2014, 85, 179
3. G. Fumagalli, D. Passarella et al. ChemPlusChem 2015, 80, 47
4. P.A. Sotiropoulou, C. Herold-Mende, D. Passarella et al. Drug Discovery Today 2014, 19, 1547
5. G. Fumagalli, D. Passarella et al. ChemPlusChem 2015, 9, 1380
6. G. Fumagalli, M.S. Christodoulou, D. Passarella et al. Org. Biomol. Chem. 2017 DOI: 10.1039/c6ob02591a
7. G. Fumagalli, M.S. Christodoulou, D. Passarella et al. Paper submitte
Natural products as building blocks and leads for the synthesis of new anticancer compounds
No full textThe presentation will be focused on the different ongoing projects in the field of natural products with the aim to forge a possible collaboration in the frame of interdisciplinary projects. At this period three different research approaches are being developed using Natural products as subject: a) synthesis of new self-assembling compounds obtained by modification of cyclopamine, paclitaxel, podophyllotoxin, camptothecin and epothilone A;1-3 b) design and synthesis of new hybrid compounds;4 c) target and diversity-oriented synthesis.5 The final aim is the discovery of new anticancer compounds, the improvement of the biological activity or the faciliting of the delivery.6 References:
[1]. Fumagalli G., Passarella D. et al. (2015), ChemPlusChem DOI: 10.1002/cplu.201500156
[2]. Borrelli, S., Fumagalli G.; Passarella D. et al. (2015) ChemPlusChem, 80: 47-49
[3]. Borrelli, S., Passarella D. et al. (2014) Eur.J.Med.Chem (2014), 85: 179-190
[4]. Marucci C., Passarella D, manuscript to be submitted
[5]. Christodoulou M., Calogero F., Passarella D. et al. (2015), Eur.J.Med.Chem 92: 766-775 and refs therein
[6]. Christodoulou M., Passarella, D. et al. (2014) Drug Discovery Today 19, 1547 – 156
Chemical Approaches to Targeting Cancer
No full textThe presentation will regard the efforts of the last years in the fields of the synthesis of anticancer compounds. Two different approaches will be discussed. The first one is based on the use of anticancer natural products as building blocks or as lead compounds.1 Chemical modifications permits the generation of small libraries of new compounds with the aim to find new biological activity, to improve the delivery and to help the understanding of the biological mechanisms.2 For what regards the delivery, preliminary results in the field of the nanoassemblies will be discussed.3
The second approach regards the de novo synthesis of new compounds on the base of isosteric substitutions and scaffold decoration of known totally synthetic anticancer compounds guided by modeling studies.4
The considered biological targets include: Tubulin, Topoisomerases, HDAC, Tyrosine Kinases (cMet, Abl), p53, Sirtuin, Hedgehog.
The recent results in the field of “in situ” target guided synthesis will be presented for the case of tubulin5 and Abl tyrosine kinase.
The discussion will take into consideration the coordination of two COST network projects regarding the inhibition of Angiogenesis6 and the targeting of drug resistance in Cancer Stem Cells.7
1. For a recent example see: M. S. Christodoulou , F. Zunino, V. Zuco, S. Borrelli, D. Comi, G. Fontana, M. Martinelli, J. Lorens, L. Evensen, M. Sironi, S. Pieraccini, L. Dalla Via, O. M. Gia, D. Passarella “Camptothecin-7-yl-methanthiole: Semisynthesis and Biological Evaluation”
ChemMedChem DOI: 10.1002/cmdc.201200322
2. E. Riva, M. Mattarella, S. Borrelli, M. S. Christodoulou, D. Cartelli, M. Main, S. Faulkner, D. Sykes, G. Cappelletti, J. S. Snaith, D. Passarella ”Preparation of Fluorescent Tubulin Binders”
ChemPlusChem. Accepted for publication
3. S. Borrelli, F. Dosio, D. Passarella unpublished results
4. For a recent example see: F. Arioli, S. Borrelli, F. Colombo, F. Falchi, I. Filippi, E. Crespan, A. Naldini, G. Scalia, A. Silvani, G. Maga, F. Carraro, M. Botta, D. Passarella “N-[2-Methyl-5-(triazol-1-yl)phenyl]pyrimidin-2-amine as a Scaffold for the Synthesis of Inhibitors of Bcr-Abl”
ChemMedChem 2011, 6, 2009 - 2018
5. For the case of tubulin see: G. Cappelletti, D. Cartelli, B. Peretto, M. Ventura, M. Riccioli, F. Colombo, J. S. Snaith, S. Borrelli, D. Passarella “Tubulin-guided dynamic combinatorial library of thiocolchicine-podophyllotoxin conjugates”
Tetrahedron 2011, 67, 7354 – 7357
6. COST Action CM0602 “Inhibitors of Angiogenesis: Design, Synthesis and Biological Exploitation” – www.angiokem.org
7. COST Action CM1106 “Chemical Approaches to Targenting Drug Resistance in Cancer Stem Cells” – www.stemchem.or
The Role of Commercial Banks and Financial Intermediaries in the New Consensus Macroeconomics (NCM): A Preliminary and Critical Appraisal of Old and New Models
No full textGiuseppe Fontana and Marco Veronese Passarella in this chapter, entitled, ‘Aggregate Demand, Money and Finance in the New Consensus Macroeconomics: a Critical Appraisal’, critically assess the ‘New Consensus Macroeconomics’ (NCM) theory and its recent developments. Building on the Wicksellian ‘two-interest rates model’, the NCM highlights the role of interest rates in the transmission mechanism of monetary policy, whereas monetary aggregates are treated as residual variables. However, in contrast with Wicksell’s theory, banks and financial institutions are usually neglected in the NCM theory. As a result, the financial instability and recurrent banking crises of modern economies have received little attention in modern macroeconomics. This chapter has three main goals. First, it aims to provide a critical analysis of the original NCM model and some recent developments. Second, it aims to show that few amendments to it are sufficient to account for the financial instability and banking crises of real-world economies. Third, it shows that some important policy-making conclusions logically follow once the role of banks, credit and finance is properly taken on board
Horizontal Runup and Seagrass Beach Cast-litters: Modelling and Observations
No full textPassarella, M.; Ruju, A.; De Muro, S., and Coco, G., 2020. Horizontal runup and seagrass beach cast-litters: Modelling and observations. In: Malvárez, G. and Navas, F. (eds.), Global Coastal Issues of 2020. Journal of Coastal Research, Special Issue No. 95, pp. 143-147. Coconut Creek (Florida), ISSN 0749-0208.
We collected measurements of wave-driven swash on a beach characterized by the presence and accumulation of seagrass beach-cast litter (the so-called banquette). Beach surveys showed that this deposit can drastically steepen the foreshore thus affecting wave dynamics. This work explores the relationship between vertical and horizontal swash time series, in a previously unreported case of seagrass wrack deposits under mild to moderate incoming waves. The results from the field measurements, obtained by video imagery time stack analysis, show that the seagrass deposits influence wave runup. The horizontal runup extent can be reduced when compared with a nearby seagrassfree profile under the same incoming waves. The horizontal runup in case of seagrass presence seems to be approximately one-third of the seagrass absence case. The ratio between observed vertical and horizontal swash, when seagrass deposits are present, is almost 3.5 times the seagrassfree case. The SWASH model was used to extend the analysis beyond our field observations. A number of possible wave forcing scenarios were run on both the seagrass-rich and the seagrass-free profiles. Differences between the cases of seagrass presence and absence show that the horizontal wave runup in case of seagrass deposition can be largely reduced. Using observations and modelling, we show that the seagrass deposits on the beach face and berm inhibit the horizontal runup and so affect one of the key components necessary to predict coastal inundation and to manage coastal areas especially considering ongoing changes in the mean sea level
Girolamo Cardano e il Liber de orthographia
No full textedizione critica, con traduzione e note, del trattato "de orthographia" di G. Cardan
Sulla valutazione dei consumi idropotabili in un insediamento turistico: indagine con utilizzo di nuovi dati sperimentali
No full textUnconventional Monetary Policies from Conventional Theories: Modern Lessons for Central Bankers
No full textThe aim of this paper is to provide a critical review of some recent developments in macroeconomics. We discuss the introduction of financial frictions in New Keynesian models, which is said to account for the increasing influence of financial markets, institutions and products in real-world economies. For this purpose, we compare the macro dynamics of a benchmark NCM-DSGE model with the behaviour of the same model augmented with a financial accelerator mechanism. Our simulation exercises show that the financial accelerator mechanism can be regarded as an effective, though indirect, way to account for hysteresis in potential output. A fundamental policy corollary follows that central banks should pursue financial stability, rather than price stability, and target current output growth, rather than output gap. Such an unconventional result is obtained by a simple macroeconomic amendment to an otherwise conventional NCM-DSGE model
Aula trinitatis haec est mater innocentiae : Monumenti della disputa ariana?
No full textIl contributo esamina le fasi salienti della controversia ariana integrando tra le fonti della ricostruzione storiografica quelle epigrafiche e iconografiche.
Il risultato cui si perviene restituisce una situazione assai più fluida dell'evolversi del dibattito cristologico, consigliando del pari un effettivo ridimensionamento della sua portata nella vita delle Chiese antiche
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