Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline

In early studies, we have reported the antinociceptive profile of (-)-spectaline, a piperidine alkaloid from Cassia spectabilis. The present study describes the synthesis, the antinociceptive and anti-inflammatory activities of a series of 2,3,6-trialkyl-piperidine alkaloids: the natural (-)-3-O-acetyl-spectaline (LASSBio-755) and ten semi-synthetic spectaline derivatives. Structure-activity relationship (SARs) studies were performed. The structures of all synthesized derivatives were confirmed by means of nuclear magnetic resonance. Compounds were evaluated for their analgesic (acetic acid-induced mouse abdominal constrictions, hot-plate test, formalin-induced pain test) and some of them for the anti-inflammatory activities (carrageenan-induced rat paw edema test). The pharmacological results showed that several of the new compounds given orally at a dose of 100 mu mol/kg significantly inhibited the acetic acid-induced abdominal constrictions, but they were less active than (-)-spectaline. LASSBio-755 and LASSBio-776 were the most actives with 37% and 31.7% of inhibition. In the formalin-induced pain only LASSBio-776 was able to inhibit by 34.4% the paw licking response of the inflammatory phase, (-)-spectaline and LASSBio-755 did show any activity. In the carrageenan-induced rat paw edema, only (-)-spectaline exhibited an anti-inflammatory profile, showing an ED(50) value of 56.6 mu mol/kg. Our results suggest different mechanisms of action for the analgesic activity observed for LASSBio-776 (3-O-Bocspectaline), LASSBio-755 (3-O-acetyl-spectaline) and (-)-spectaline (LASSBio-754). The antinociceptive profile of some of the semi-synthetic spectaline derivatives extends our research concerning the chemical and pharmacological optimization of isolated natural products in the search of new drug candidates from brazilian biodiversity.

Short-term variability of copepod abundance in Jurumirim Reservoir, São Paulo, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Longitudinal distribution of Copepoda populations in the transition zone of Paranapanema River and Jurumirim Reservoir (São Paulo, Brazil) and interchange with two lateral lakes.

Longitudinal changes in composition, abundance, and distribution of copepods were studied at the transition zone of Paranapanema River-Jurumirim Reservoir (SP, Brazil). The interchange of biotic material between marginal lakes and the river system was also examined. Water samples were obtained from 6 stations along a stretch of 13 km of the Paranapanema River, from an upstream reach with high water velocity up to the river mouth into Jurumirim Reservoir. Two other sites in lateral lakes were also sampled. Nine copepod taxa were identified: 3 calanoids (Argyrodiaptomus furcatus Sars, Notodiaptomus iheringi Wright, and N. conifer Sars) and 6 cyclopoids (Eucyclops Claus, Microcyclops Claus, Mesocyclops longisetus Thiébaud, Thermocyclops decipiens Fischer, T. minutus Lowndes, and Paracyclops Claus). Harpacticoids were also collected. Calanoid and cyclopoid nauplii and copepodids, and harpacticoids were the most abundant organisms. In general, there was a longitudinal decrease in copepod abundance, whereas an increase was detected near the lakes. The abundance of most copepods was inversely correlated with current velocity and suspended solids. Higher abundance was observed in the river main course during the rainy season, during which there is a higher connectivity between the lakes and the main river. This promotes exportation of biologic material from marginal lakes to the river system, a biotic exchange reflecting the importance of marginal lakes to the river community structure.

Interaction of biologically-relevant peptides with membrane model systems

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)