Fabrizio Manetti

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Pharmacophoresthree-dimensional (3D) arrangements of essential features enabling a molecule to exert a particular biological effectconstitute a very useful tool in drug design both in hit discovery and hit-to-lead optimization process. Two basic approaches for pharmacophoric model generation can be used by chemists, depending on the availability or not of(More)
RET tyrosine kinase (TK) oncoproteins are potential targets for anticancer therapy. However, the search for novel RET inhibitors has been hampered by the lack of a 3D structure of the receptor. In this study, the "open" and the "closed" structure of the RET TK catalytic domain have been built by homology modeling techniques. The structures were validated by(More)
The HIV-1 nucleocapsid protein-7 (NCp7) is a highly basic, small zinc-binding protein involved in both deoxyribonucleic (DNA) and ribonucleic (RNA) acids annealing and in viral particle maturation including genome encapsidation, with an additional chaperoning activity toward reverse transcriptase by promoting the two obligatory strand transfers during(More)
HIV-1 integrase (IN) is an essential enzyme for viral replication and represents an intriguing target for the development of new drugs. Although a large number of compounds have been reported to inhibit IN in biochemical assays, no drug active against this enzyme has been approved by the FDA so far. In this study, we report, for the first time, the use of(More)
1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken. By selecting the optimal substitution patterns for the phenyl rings at N1 and C5(More)
The HIV-1 nucleocapsid protein (NCp7) is an emerging target for antiretroviral therapy. Five hits have been reported to inhibit the NCp7-viral nucleic acids interaction at micromolar concentrations. We used two computationally refined structures of NCp7 as receptors to propose a reliable binding pose for these compounds, by means of computational methods.(More)
Extracellular signal-regulated kinase 8 (ERK8) has been already implicated in cell transformation and in the protection of genomic integrity and, therefore, proposed as a novel potential therapeutic target for cancer. In the absence of a crystal structure, we developed a three-dimensional model for its kinase domain. To validate our model we applied a(More)
Hedgehog (Hh) is a critical regulator of adipogenesis. Extracellular vesicles are natural Hh carriers, as illustrated by activated/apoptotic lymphocytes specifically shedding microparticles (MP) bearing the morphogen (MP(Hh+)). We show that MP(Hh+) inhibit adipocyte differentiation and orientate mesenchymal stem cells towards a pro-osteogenic program.(More)
The HIV-1 entry process is an important target for the design of new pharmaceuticals for the multidrug therapy of AIDS. A lot of polyanionic compounds, such as polysulfonated and polysulfated, are reported in the literature for their ability to block early stages of HIV-1 replication. Several studies have been performed to elucidate the mechanism of the(More)
Sulfonated distamycin (Suradista) derivatives exhibit anti-HIV-1 activity by inhibiting the binding of the viral envelope glycoprotein gp120 to its receptor (CD4). With the aim to propose a possible binding mode between Suradistas and the CD4 macromolecule, molecular docking experiments, followed by energy minimization of the complexes thus obtained, were(More)