12 research outputs found
Polimeri iper-ramificati a potenziale attivitĂ biologica
Nel corso di una ricerca volta all’individuazione di nuovi inibitori dell’HIV-1 integrasi (IN),
sono stati sintetizzati e sottoposti a valutazione biologica l’acido 5,6-diidrossiindolo-2-
carbossilico (DHICA), un intermedio nella biosintesi della melanina, ed una serie di suoi
derivati.
Questi composti erano stati progettati come analoghi conformazionalmente rigidi della
porzione acrilica dell’ estere feniletilico dell’acido caffeico (CAPE). E’ risultato interessante
il fatto che diversi derivati hanno mostrato attività inibitoria nei confronti dell’enzima HIV-1
IN a concentrazioni micromolari
Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?
Nerve growth factor (NGF) was the first-discovered member of the neurotrophin family, a class of bioactive molecules which exerts powerful biological effects on the CNS and other peripheral tissues, not only during development, but also during adulthood. While these molecules have long been regarded as potential drugs to combat acute and chronic neurodegenerative processes, as evidenced by the extensive data on their neuroprotective properties, their clinical application has been hindered by their unexpected side effects, as well as by difficulties in defining appropriate dosing and administration strategies. This paper reviews aspects related to the endogenous production of NGF in healthy and pathological conditions, along with conventional and biomaterial-assisted delivery strategies, in an attempt to clarify the impediments to the clinical application of this powerful molecule
Ricerca di nuovi inibitori selettivi dell'HIV-1 integrasi
L'obiettivo di questo lavoro era quello di individuare nuovi potenziali farmacofori attraverso
un approccio di virtual screening utilizzando il NCI database e seguendo strategie di
structure-based drug design mediante l'utilizzo della struttura cristallina dell'HIV-1 IN cocristallizzato
con un inibitore. Sono stati così ottenuti ed ottimizzati diversi spezzoni
farmacoforici che sono stati incorporati su vari anelli aromatici ed eteroaromatici
Studi su indoli Beta-dichetoacidi come inibitori dell'HIV-1 integrasi: progettazione, sintesi, studi SAR, cristallografia e docking
Di recente, una categoria di composti recanti uno spezzone Beta-dichetoacido (I) è stata indipendentemente individuata da
ricercatori della Shionogi e della Merck come una nuova classe di inibitori selettivi dell'HIV-
1 IN ad attivitĂ antivirale.
In questo lavoro è stato confermato che il farmacoforo Beta-dichetoacido è importante per la
selettività verso lo strand transfer ma che questa non è sufficiente per l'attività  antivirale. E'
stato inoltre dimostrato che la porzione aromatica gioca un ruolo di particolare importanza
nell'attivitĂ inibitoria
ICAROS (Italian survey on CardiAc RehabilitatiOn and Secondary prevention after cardiac revascularization): Temporary report of the first prospective, longitudinal registry of the cardiac rehabilitation network GICR/IACPR
Application of near-infrared spectroscopy for frozen-thawed characterization of cuttlefish (Sepia officinalis)
Few works to date have reported the application of near-infrared spectroscopy (NIRS) for the characterization and authentication of cephalopods. This study investigated the feasibility of a portable NIRS instrument for the non-destructive freshness evaluation of fresh (F) and frozen-thawed (FT) cuttlefish (Sepia officinalis). Samples were examined by chemical, microbiological and sensorial analyses, during 13 days of conservation at 3 \ub0C. The spectral data were collected on lateral mantle of cuttlefish, and different partial least squares discriminant analyses (PLS-DA) were applied for classification purposes. The interpretation of spectra was also investigated by applying the specific water coordinates, using aquaphotomics. Few significant differences in the wet chemistry and microbiological data were detected between F and FT during storage. The quality index method and microbiological analyses suggested similar behavior between F and FT samples until to near 9 days of shelf life. PLS-DA models with the spectral range 900\u20131650 nm achieved a classification precision of 0.91 between F and FT, while the performances for the prediction of storage days were less effective. The results of aquaphotomics plotted in aquagrams were suitable for the interpretation of the main physicochemical changes of cuttlefish throughout the shelf life. The water coordinates suggested a different molecular conformation of water species in the FT than F samples, with more free water molecules and a lower amount of bound species and the water solvation shell, respectively
A Time-Course Study of the Expression Level of Synaptic Plasticity-Associated Genes in Un-Lesioned Spinal Cord and Brain Areas in a Rat Model of Spinal Cord Injury: A Bioinformatic Approach
“Neuroplasticity” is often evoked to explain adaptation and compensation after acute lesions of the Central Nervous System (CNS). In this study, we investigated the modification of 80 genes involved in synaptic plasticity at different times (24 h, 8 and 45 days) from the traumatic spinal cord injury (SCI), adopting a bioinformatic analysis. mRNA expression levels were analyzed in the motor cortex, basal ganglia, cerebellum and in the spinal segments rostral and caudal to the lesion. The main results are: (i) a different gene expression regulation is observed in the Spinal Cord (SC) segments rostral and caudal to the lesion; (ii) long lasting changes in the SC includes the extracellular matrix (ECM) enzymes Timp1, transcription regulators (Egr, Nr4a1), second messenger associated proteins (Gna1, Ywhaq); (iii) long-lasting changes in the Motor Cortex includes transcription regulators (Cebpd), neurotransmitters/neuromodulators and receptors (Cnr1, Gria1, Nos1), growth factors and related receptors (Igf1, Ntf3, Ntrk2), second messenger associated proteins (Mapk1); long lasting changes in Basal Ganglia and Cerebellum include ECM protein (Reln), growth factors (Ngf, Bdnf), transcription regulators (Egr, Cebpd), neurotransmitter receptors (Grin2c). These data suggest the molecular mapping as a useful tool to investigate the brain and SC reorganization after SCI
Design and Synthesis of Novel Indole ‚-Diketo Acid Derivatives as HIV-1 Integrase Inhibitors’
Diketo acids such as S-1360 (1A) and L-731,988 (2) are potent and selective inhibitors of HIV-1
integrase (IN). A plethora of diketo acid-containing compounds have been claimed in patent
literature without disclosing much biological activities and synthetic details (reviewed in
Neamati, N. Exp. Opin. Ther. Pat. 2002, 12, 709-724). To establish a coherent structureactivity
relationship among the substituted indole nucleus bearing a â-diketo acid moiety, a
series of substituted indole-â-diketo acids (4a-f and 5a-e) were synthesized. All compounds
tested showed anti-IN activity at low micromolar concentrations with varied selectivity against
the strand transfer process. Three compounds, the indole-3-â-diketo acids 5a and 5c, and the
parent ester 9c, have shown an antiviral activity in cell-based assays. We further confirmed a
keto-enolic structure in the 2,3-position of the diketo acid moiety of a representative compound
(4c) using NMR and X-ray crystallographic analysis. Using this structure as a lead for all of
our computational studies, we found that the title compounds extensively interact with the
essential amino acids on the active site of IN