PubMed Health⌕ Search

Biomedical subjects

Claudia Mugnaini

Publications and source records attributed to Claudia Mugnaini.

9 recordsLinked to original sources
PubMed2006

Synthesis and biological evaluation of 4-alkylamino-6-(2-hydroxyethyl)-2-methylthiopyrimidines as new rubella virus inhibitors.

In the search for new chemotherapeutic agents useful against Rubella virus (RV) infections, a solution-phase parallel approach for the synthesis of a small library of 4-alkylamino-6-(2-hydroxyethyl)-2-methylthiopyrimidines has been set up, based on previous results from our research group. Biological evaluation of the newly synthesized compounds pointed out their interesting properties as anti-RV agents with IC(50) values in the micromolar range.

Animals↗
PubMed2006

Simplified analogues of immucillin-G retain potent human purine nucleoside phosphorylase inhibitory activity.

A set of deazaguanine derivatives 1-3 targeting human purine nucleoside phosphorylase (hPNP) have been designed and synthesized. The new compounds are characterized by the presence of a structurally simplified "azasugar" motif to be more easily accessible by chemical synthesis than previous inhibitors. In the enzymatic assays, some of the new derivatives proved to be able to inhibit hPNP at low nanomolar concentration, thereby showing the same inhibitory potency in vitro as immucillin-H (IMH). Molecular docking experiments revealed a binding mode to hPNP essentially identical to that of IMH. As a result, the lower in vivo activity exhibited by 1d, compared with that exhibited by IMH, might be ascribed to differences in the pharmacokinetic, rather than pharmacodynamic, profile between these compounds. Derivatives 1a, 1d, and 2c emerged as the most active compounds within this new set and may represent interesting leads in the search for novel hPNP inhibitors.

Antineoplastic Agents↗
PubMed2005

Parallel solution-phase and microwave-assisted synthesis of new S-DABO derivatives endowed with subnanomolar anti-HIV-1 activity.

A simple and efficient methodology for the parallel solution-phase synthesis has been set up to obtain a series of thiouracils, in turn selectively S-benzylated under microwave irradiation to give new S-DABOs. Biological screening led to the identification of compounds with nanomolar activity toward both the highly purified recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) enzyme (wild-type and mutants) and wild-type (wt) and mutant HIV-1 strains. In particular, 20 was found to be the most potent S-DABO reported so far (ID50 = 26 nM toward the isolated wt enzyme) with subnanomolar activity toward both the wt and the pluriresistant virus (IRLL98) HIV-1 strain (EC50 < 0.14 nM and EC50 = 0.22 nM, respectively). Molecular modeling calculations were also performed to investigate the binding mode of such compounds onto the non-nucleoside reverse transcriptase inhibitor binding site and to rationalize the relationships between their chemical structure and activity values toward wt RT.

Anti-HIV Agents↗
PubMed2005

A new linker for anchoring/masking primary amines on solid support.

A polymer-supported diketone was synthesized and used to fully protect/mask primary amines by the formation of a pyrrole ring. Various reactions can be performed on this system which then can be cleaved with full restoration of the amine functionality. The resin can also be recycled at least once without loss of purity of the final compound. [structure: see text]

Amines↗
PubMed2005

Combinatorial chemistry as a tool for targeting different stages of the replicative HIV-1 cycle.

In the present era, acquired immunodeficiency syndrome (AIDS) is the most fatal disorder for which no completely successful chemotherapy has been developed so far. The pandemic spread of this disease has prompted an unprecedented scientific and clinical effort to understand and combat it. A number of targets has been identified to stop the replication of the virus at different stages of its life cycle: Reverse Transcriptase (RT), protease (PR) and CCR5 are the most promising targets. Although highly active antiretroviral therapy (HAART) has been effective in reducing the mortality and morbidity in recent years, adverse side effects of the chemotherapy, patient non-compliance and the development of viral resistance remain major problems. With the aim to find better drug candidates with minor adverse side effects in recent years, several groups have investigated combinatorial approaches for the generation of libraries of HIV PR inhibitors while only few contributions to the preparation of libraries of HIV Reverse Transcriptase (RT) and CCR5 inhibitors are available. This review summarizes the recent developments of combinatorial chemistry in this area.

Animals↗
PubMed2003

Precise structure activity relationships in asymmetric catalysis using carbohydrate scaffolds to allow ready fine tuning: dialkylzinc-aldehyde additions.

The ready construction of 24 stereochemically and functionally diverse carbohydrate ligand structures from a core D-glucosamine scaffold has allowed the evaluation of broad ranging structure activity relationships in ligand accelerated zincate additions to aldehydes, with variations in deltadeltaG+/+(R-S) of up to 5650 J mol(-1) that create opposing senses of asymmetric induction and that are consistent with models based on several ligand X-ray structures and molecular mechanics analysis. Factorial analysis of enantioselectivity using key dihedral angles and steric volume on N-2 also highlight the potential for the use of factorial design in ligand construction.

Aldehydes↗
PubMed2003

Research on L-nucleosides. Synthesis and biological evaluation of a series of L- and D-2',3'-dideoxy-3'-[tris(methylthio)methyl]-beta-pentofuranosyl nucleosides.

Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3'-tris(methylthio)methyl group allowed a good stereoselectivity level. All the compounds of both enantiomeric series showed high IC(50) values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK. In order to overcome possible problems related to the first phosphorylation step and to facilitate the penetration of the molecule through the cellular membrane, a monophosphate prodrug containing a long lipophilic chain was synthesized. No appreciable antiviral activity was exhibited by this molecule.

3T3 Cells↗