Design, synthesis, and biological evaluation of a second generation of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as potent and selective A2A adenosine receptor antagonists.

New A2A adenosine receptor antagonists in the series of pyrazolo[4, 3-e]-1,2,4-triazolo[1,5-c]pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A2A compared to rat A1 and human A3 receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A1 and A2A adenosine receptors. They showed very good affinity (Ki = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA1 and hA3 (compound 5h: rA1/rA2A = 787, hA3/rA2A > 10 000). These important findings make this new series of compounds the first really selective for A2A adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

[Microbiological characterization of solid wastes and aerosol in a municipal solid waste landfill site]. / Caratterizzazione microbiologica dei rifiuti solidi e degli aerosol che si generano nelle discariche controllate di rifiuti solidi urbani.

Authors report data about microbiological characterization of solid wastes and aerosol in the municipal solid waste landfill site in Poiatica (RE). In solid waste samples high values of total coliform and fecal coliform were observed (10(5)-10(6) CFU/g): total bacterial counts at 22 degrees, at 36 degrees and at 44 degrees ranged from 10(7) to 10(9) CFU/g. Aerosol samples collected during waste movement in the landfill site showed values of total and fecal bacterial ranging from 10(3)-10(4) CFU/m3. Staphylococci and fungi reported the same values while streptococci, total and fecal coliform and spore evidenced lower values. Municipal solid wastes and aerosol have to be considered as an infective substrate: it is necessary to adopt protective barriers in occupationally exposed subjects.

Symmetry-based HIV protease inhibitors containing (S,S) or (R,R) tartaric acid core structure.

Two series of symmetry-based HIV protease inhibitors containing (S,S) or (R,R) tartaric acid core structure were prepared and tested for inhibitory property against the enzyme. All compounds showed weak antiprotease activity.