Benzoxazolone Carboxamides: Potent and Systemically Active Inhibitors of Intracellular Acid Ceramidase

The ceramides are a family of bioactive lipid‐derived messengers involved in the control of cellular senescence, inflammation, and apoptosis. Ceramide hydrolysis by acid ceramidase (AC) stops the biological activity of these substances and influences survival and function of normal and neoplastic cells. Because of its central role in the ceramide metabolism, AC may offer a novel molecular target in disorders with dysfunctional ceramide‐mediated signaling. Here, a class of benzoxazolone carboxamides is identified as the first potent and systemically active inhibitors of AC. Prototype members of this class inhibit AC with low nanomolar potency by covalent binding to the catalytic cysteine. Their metabolic stability and high in vivo efficacy suggest that these compounds may be used as probes to investigate the roles of ceramide in health and disease, and that this scaffold may represent a promising starting point for the development of novel therapeutic agents.     

Status of PRESS-MAG-O: The experimental apparatus to probe materials and phenomena under extreme conditions at Frascati

In this contribution we up-to-date the status of the PRESS-MAG-O device, a new instrument under commissioning at the INFN designed to perform magnetic and spectroscopic experiments on samples under extreme conditions. The system has been designed to work at SINBAD, the IR synchrotron radiation beamline operational at DAΦNE. The instrument, that is the result of a significant R&D, will allow performing concurrent high harmonic ac magnetic susceptibility measurements and magneto-optic experiments on a sample under high pressure, with a variable DC magnetic field in a wide temperature range. The vacuum vessel has been designed with four crossing windows to allow optical measurements in the transmission geometry on the sample loaded inside a Diamond Anvil Cell. A new superconducting miniaturized micro-SQUID gradiometer has been also developed to detect the low magnetic signal of the sample and a customized optical system has also been designed to perform IR synchrotron radiation experiments.     

Inverse compton scattering on laser beam and monochromatic isotropic radiation

Most of the known literature on inverse compton scattering (ICS) is based on earliest theoretical attempts and later approximations led by F.C. Jones and J.B. Blumenthal. We found an independent and more general analytical procedure which provide both relativistic and ultrarelativistic limits for ICS. These new analytical expressions can be derived in a straightforward way and they contain the previously reminded Jones’ results. Our detailed solutions may be probed by already existing as well future ICS experiments.     

A FPTAS for a class of linear multiplicative problems

In this paper we consider the problem of minimizing the product of two affine functions over a polyhedral set. An approximation algorithm is proposed and it is proved that it is a Fully Polynomial Time Approximation Scheme. We will also present and computationally investigate an exact version of the algorithm.     

Cross‐linked resins functionalized with triorganotin carboxylates: synthesis,characterization and preliminary catalytic screening in transesterification

Cross‐linked polymers containing triorganotin carboxylate functionalities were synthesized from ionic exchange resins bearing carboxylic groups. The organic tin substituents selected were methyl and butyl in order to ensure different accessibility at the metal centre. The functionalization degree depends on the different substituents and strongly affects the thermal stability of the final product. Catalytic screenings were performed in order to assess the activity of the above resins in transesterification reactions, using ethyl acetate as a substrate, together with differently hindered alcohols. The results obtained point to a negligible role of the bulkiness of tin substituents with a small contribution of the metal atom Lewis acidity in the conversion of the primary alcohol, whereas with secondary and tertiary alcohols the steric hindrance of the reagent strongly affects the conversion of the reacting alcohol. The transesterification process takes place at the liquid–solid interface, so that the catalyst grafted to an insoluble solid support can be completely removed by simple filtration. Copyright © 2005 John Wiley & Sons, Ltd.     

A practical entry to C18-constrained-E-ring analogues of methyllycaconitine (MLA): a concise new stereoselective approach to 8-oxa-decahydroisoquinolines accompanied by a simple microwaves-assisted synthesis of the succinimidobenzoate appendage of MLA

A Mannich-type intramolecular cyclization afforded access to a 8-oxa-decahydroisoquinoline heterocyclic system. Good stereoselectivity was observed. A promising microwave-assisted synthesis of the methylsuccinimidobenzoate moiety of methyllycaconitine has also been carried out.     

Synthesis and characterization of new polystyrenes containing tributyltin moieties linked to the aromatic ring through a methylenic spacer

Novel polymeric derivatives bearing tributyltin carboxylate moieties in the side chain were synthesized. The coordination at tin in solution and in the solid state was investigated by both Sn‐NMR and FT‐IR: the metal atom appears completely tetracoordinated in chloroform solution, while in the solid state all polymeric products exhibit both tetra‐ and pentacoordination at tin, the latter increasing with the amount of tin containing units. No evidence of tin leaching by hydrolysis of the organometallic ester was observed for these materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5372–5383, 2004