Estimation of the PPARα agonism of fibrates by a combined MM-docking approach.

Fibrates are peroxisome proliferator-activated alpha receptor (PPARα) activators derived from fibric acid and are the most clinically used therapeutics in the treatment of hypertriglyceridemia. Recently, we reported a computational approach for the investigation of the binding properties of fibrates, characterized by similar carboxylic heads but differing in the size and orientation of the hydrophobic portion. This procedure is based on a combination of standard docking and molecular mechanics approaches to better describe the adaptation of the protein target to the bound ligand.

Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus.

Bovine lactoferrin (bLf) is a multifunctional glycoprotein that plays an important role in innate immunity against infections, including influenza. Here we have dissected bLf into its C- and N-lobes and show that inhibition of influenza virus hemagglutination and cell infection is entirely attributable to the C-lobe and that all major virus subtypes, including H1N1 and H3N2, are inhibited. By far-western blotting and sequencing studies, we demonstrate that bLf C-lobe strongly binds to the HA(2) region of viral hemagglutinin, precisely the highly conserved region containing the fusion peptide.

Binding of GSH conjugates to π-GST: a cross-docking approach.

The high degree of flexibility characterizing the members of the GST protein family is supposed to be an evolution-resolved feature related to the detoxifying role of these enzymes. Many evidences suggest that overexpression of these enzymes may be implicated in the development of acquired resistance to antitumor agents. Among the most effective GST inhibitors, GSH conjugates have been found to be particularly promising because of their low toxicity.

Prediction of the PPARα agonism of fibrates by combined MM-docking approaches.

Fibrates are peroxisome proliferator-activated alpha receptor (PPARα) activators derived from fibric acid and are the most clinically used therapeutics in the treatment of hypertriglyceridemia. Long standing studies on these drugs have accumulated a large body of experimental data about their biological activity and, more recently, on the molecular mechanism mediating their PPARα agonism. An immense interest for the discovery of new fibrates with improved potency and PPARα selectivity has stimulated many investigations toward a deeper understanding of structure-activity relationships controlling their activity.

N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase.

A series of N-substituted acetamidines and 2-methylimidazole derivatives structurally related to W1400 were synthesized and evaluated as Nitric Oxide Synthase (NOS) inhibitors. Analogs with sterically hindering isopropyl and phenyl substituents on the benzylic carbon connecting the aromatic core of W1400 to the acetamidine nitrogen, showed good inhibitory potency for nNOS (IC(50)=0.2 and 0.

Synthesis and biological evaluation of 2-heteroarylthioalkanoic acid analogues of clofibric acid as peroxisome proliferator-activated receptor alpha agonists.

A series of 2-heteroarylthioalkanoic acids were synthesized through systematic structural modifications of clofibric acid and evaluated for human peroxisome proliferator-activated receptor alpha (PPARalpha) transactivation activity, with the aim of obtaining new hypolipidemic compounds. Some thiophene and benzothiazole derivatives showing a good activation of the receptor alpha were screened for activity against the PPARgamma isoform. The gene induction of selected compounds was also investigated in the human hepatoma cell line.