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A docking protocol aimed at obtaining a consistent qualitative and quantitative picture of binding for a series of hERG channel blockers is presented. To overcome the limitations experienced by standard procedures when docking blockers at hERG binding site, we designed a strategy that explicitly takes into account the conformations of the channel, their possible intrinsic symmetry, and the role played by the configurational entropy of ligands. The protocol was developed on a series of congeneric sertindole derivatives, allowing us to satisfactorily explain the structure-activity relationships for this set of blockers. In addition, we show that the performance of structure-based models relying on multiple-receptor conformations statistically increases when the protein conformations are chosen in such a way as to capture relevant structural features at the binding site. The protocol was then successfully applied to a series of structurally unrelated blockers.

Molecular knowledge of hERG blocking liability can offer the possibility of optimizing lead compounds in a way that eliminates potentially lethal side effects. In this study, we computationally designed, synthesized, and tested a small series of "minimally structured" molecules. Some of these compounds were remarkably potent against hERG (6, IC(50) = 2.4 nM), allowing us to identify the minimal structural requirements for hERG blocking liability.

Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. To confront AD, an innovative strategy is to design single chemical entities able to simultaneously modulate more than one target. Here, we present compounds that inhibit acetylcholinesterase and NMDA receptor activity. Furthermore, these compounds inhibit AChE-induced Abeta aggregation and display antioxidant properties, emerging as lead candidates for treating AD.

The chemical composition of the volatile fractions from leaves of three Olea europaea L. cultivars (Leccino, Frantoio, and Cipressino) harvested at two different times of the year were examined by GC and GC-MS. The results showed a high content of aliphatic aldehydes in the three cultivars during both harvesting periods and an increase of (E)-2-hexenal (an aldehyde with high antimicrobial properties) percentage from July to November.

Some essential oils obtained from the branches of four Pinus species (P. pinea L., P. halepensis Mill., P. pinaster Soil in Ait., and P. nigra Arnold) have been evaluated for their acaricidal activity by aerial diffusion against the stored food mite Tyrophagus putrescentiae (L.). All the essential oils showed a good efficacy, but P. pinea oil and its two constituents 1,8-cineole and limonene were the most effective compounds, showing 100% acaricidal activity at 8 microL; 1,8-cineole showed the same activity at 6 microL.

The productive potential of two different ecotypes of Rosmarinus officinalis (Cevoli and Lunigiana) cultivated in the littoral area near Pisa (northern Tuscany, Italy) and the differences in the yield and composition of the essential oils of leaves, flowers, and stems obtained from different positions of the plants were used to characterize the two ecotypes. The Cevoli ecotype plant produced the highest yield of dry matter (221 g plant-1) in comparison to the Lunigiana ecotype (72 g plant-1). There were significant differences in dry matter production of different organs of both ecotypes. The essential oil contents of Cevoli and Lunigiana ecotypes were similar. In contrast, the oil contents of the different plant parts showed marked differences. The apical part of the plant and the leaves gave the highest essential oil yields. The major difference between the oils of the two ecotypes consisted in the 1,8-cineole contents (6.6 and 37.9% in Cevoli and Lunigiana, respectively). The Cevoli ecotype was determined to be the most suitable for essential oil extraction because it was characterized by a preponderance of flowers and leaves in the apical portion. The Cevoli ecotype could be classifited as an alpha-pinene chemotype, whereas Lunigiana is a 1,8-cineole chemotype.