21,511 research outputs found
In vitro and in silico studies of polycondensed diazine systems as anti-infective agents
No full textInfective diseases caused by protozoarian agents are still relevant today
more than ever. In fact, they represent the first cause of death all over the world
with seventeen millions victims every year. The development of drug resistance
and the broad diffusion of these pathologies make actual the research of new
molecules able to act as selective and effective anti-infective chemotherapics.[1]
Recently several polycondensed
diazine derivatives, by means 1,3-dipolar
cycloaddition, reactions [2, 3] were
synthesized.
A broad selection of these
compounds chosen with a wide pattern of
substitutions were submitted to biological
in vitro screening against Plasmodium
falciparum, Leishmania Infantum,
Trypanosoma brucei e Trypanosoma
cruzi, and they resulted active at
micromolar level. In order to identify
molecular targets able to explain the
mechanism of action of these compounds,
we performed Induced Fit Docking/MM-GBSA modeling studies. The obtained
results give interesting indications about the probable mechanism of action of the
most active compounds.
[1] M. Gonzaalez, H. Cerecetto, Expert Opinion on Therapeutic Patents, 21,
2011, 699-715.
[2] A. Lauria, A. Guarcello, G. Dattolo, A.M. Almerico, Tetrahedron Lett., 49,
2008, 1847-1850.
[3] A. Lauria, A. Guarcello, G. Macaluso, G. Dattolo, A.M. Almerico,
Tetrahedron Lett., 50, 2009, 7333-7336
Investigation of flap motions in wild type and M46I/G51D Mutant HIV-1 Protease by molecular dynamics studies
No full textDesign and Synthesis of Annelated Pyrrolo-pyrimidines as Leads for New Antitumor Agents.
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Chemometric Methods in the Study of HIV-1 Inhibitors and Resistance Induced by Mutations
No full textMolecular modelling studies on dopamine-amino acid conjugates as potential dopaminergic modulators
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Zinc complexes as fluorescent chemosensors for nucleic acids: New perspectives for a "boring" element
No full textZinc(ii) complexes are effective and selective nucleic acid-binders and strongly fluorescent molecules in the low energy range, from the visible to the near infrared. These two properties have often been exploited to quantitatively detect nucleic acids in biological samples, in both in vitro and in vivo models. In particular, the fluorescent emission of several zinc(ii) complexes is drastically enhanced or quenched by the binding to nucleic acids and/or upon visible light exposure, in a different fashion in bulk solution and when bound to DNA. The twofold objective of this perspective is (1) to review recent utilisations of zinc(ii) complexes as selective fluorescent probes for nucleic acids and (2) to highlight their novel potential applications as diagnostic tools based on their photophysical properties. This journal i
A QSAR study investigating the potential anti-HIV-1 effect of some Acyclovir and Ganciclovir analogs
No full textA QSAR study, involving the use of alculated physical-chemical properties (TSARTM), and the use of a neural network approach (TSARTM), has been performed on the potential anti-HIV-1 activity of a series of Acyclovir and Ganciclovir analogs. Model obtained allows reliable predictions for the anti-HIV-1 activity of these derivatives, and showed that the presence of the Ganciclovir chain in triazolopyrrolopyrimidine and pyrimidopyrrolopyrimidine series seems to increase the antiviral effect
3D-QSAR Pharmacophore Modeling and in Silico Screening of new Bcl-xl Inhibitors
No full textBcl-2 proteins family members play several roles in tumoral proliferation: they inhibit proapoptotic activity during oncogenesis, support tumor cells survival, induce chemoresistance. The discovery of new small inhibitors of Bcl-xl represents a new frontier for cancer treatment. In this study, a 3D-QSAR pharmacophore model was developed, based on 42 biarylacylsulfonamides, and used to understand the structural factors affecting the inhibitory potency of these derivatives. Aromatic, negative charge, and hydrogen bond acceptor effects contribute to the inhibitory activity. The model was then employed as 3D search query to screen ZINC drug-like database in order to select new scaffolds. Finally six hits were identified. Docking study evidenced the capability of these compounds to interact with Bcl-xl receptor, and they were selected for further in vitro and in vivo assay studies
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