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Titolo: Vapor liquid equilibrium data for systems containing morpholine.

Titolo: Synthesis, biological evaluation, and three-dimensional in silico pharmacophore model for sigma1 receptor ligand based on a series of benzo[d]oxazol-2(3H)-one derivatives
Abstract: Novel benzo[d]oxazol-2(3H)-one derivatives were designed and synthesized, and their affinities against σ receptors were evaluated. On the basis of 31 compounds, a three-dimensional pharmacophore model for the σ1 receptor binding site was developed using the Catalyst 4.9 software package. The best 3D pharmacophore hypothesis, consisting of one positive ionizable, one hydrogen bond acceptor, two hydrophobic aromatic, and one hydrophobic features provided a 3D-QSAR model with a correlation coefficient of 0.89. The best hypothesis was also validated by three independent methods, i.e., the Fisher randomization test included in the CatScramble functionality of Catalyst, the leave-one-out test, and activity prediction of an additional test set. The achieved results will allow researchers to use this 3D pharmacophore model for the design and synthesis of a second generation of high affinity σ1 ligands, as well as to discover other lead compounds for this class of receptors.

Titolo: Experimental and computational simulation studies of co-polymeric nanocarriers for delivery of small interfering RNA therapeutics

Titolo: How far can you go? dendrimer-siRNA interactions analyzed by computer simulations

Titolo: Upgrading polymeric materials from post industrial rejects: a multiscale simulation approach

Titolo: Excess enthalpy calculations by means of equations of state

Titolo: Synthesis, characterization and molecular modeling of a cyclodextrin-bioconjugate as anticancer drug

Titolo: Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma
Abstract: Basal cell carcinomas (BCCs) and a subset of medulloblastomas are characterized by loss- of-function mutations in the tumor suppressor gene, PTCH1. PTCH1 normally functions by repressing the activity of the Smoothened (SMO) receptor. Inactivating PTCH1 mutations result in constitutive Hedgehog pathway activity through uncontrolled SMO signaling. Tar- geting this pathway with vismodegib, a novel SMO inhibitor, results in impressive tumor regression in patients harboring genetic defects in this pathway. However, a secondary mutation in SMO has been reported in medulloblastoma patients following relapse on vis- modegib to date. This mutation preserves pathway activity, but appears to confer resis- tance by interfering with drug binding.
Here we report for the first time on the molecular mechanisms of resistance to vismodegib in two BCC cases. The first case, showing progression after 2 months of continuous vismo- degib (primary resistance), exhibited the new SMO G497W mutation. The second case, showing a complete clinical response after 5 months of treatment and a subsequent pro- gression after 11 months on vismodegib (secondary resistance), exhibited a PTCH1 nonsense mutation in both the pre- and the post-treatment specimens, and the SMO D473Y mutation in the post-treatment specimens only. In silico analysis demonstrated that SMOG497W undergoes a conformational rearrangement resulting in a partial obstruc- tion of the protein drug entry site, whereas the SMO D473Y mutation induces a direct effect on the binding site geometry leading to a total disruption of a stabilizing hydrogen bond network. Thus, the G497W and D473Y SMO mutations may represent two different mech- anisms leading to primary and secondary resistance to vismodegib, respectively.

Titolo: Cationic carbosilane dendrimers and oligonucleotide binding: an energetic affair
Abstract: GENERATION 2 CATIONIC CARBOSILANE DENDRIMERS HOLD GREAT PROMISE AS INTERNALIZING AGENTS FOR GENE THERAPY AS THEY PRESENT LOW TOXICITY AND RETAIN AND INTERNALIZE GENETIC MATERIAL AS OLIGONUCLEOTIDE OR SIRNA. IN THIS WORK WE CARRIED OUT A COMPLETE IN SILICO STRUCTURAL AND ENERGETICAL CHARACTERIZATION OF THE INTERACTIONS OF A SET OF 2G CARBOSILANE DENDRIMERS, SHOWING DIFFERENT AFFINITY TOWARDS TWO SINGLE STRAND OLIGONUCLEOTIDE (ODN) SEQUENCES IN VITRO. OUR SIMULATIONS PREDICT THAT THESE FOUR DENDRIMERS AND THE RELEVANT ODN COMPLEXES ARE CHARACTERIZED BY SIMILAR SIZE AND SHAPE, AND THAT THE MOLECULE-SPECIFIC ODN BINDING ABILITY CAN BE RATIONALIZED ONLY CONSIDERING A CRITICAL MOLECULAR DESIGN PARAMETER: THE NORMALIZED EFFECTIVE BINDING ENERGY ΔGBIND,EFF/NEFF I.E., THE PERFORMANCE OF EACH ACTIVE INDIVIDUAL DENDRIMER BRANCH DIRECTLY INVOLVED IN A BINDING INTERACTION

Titolo: Multiscale molecular modeling for the design of materials in the nano-bio-based economy