activity Anti-dyskinetic Membrane Effects Anti-dyskinetic Anti-vira anti-allerg P a P i the database integrity agonist anti-inflammato anti-prurit anti-eczemat anti-seborrhoeic and anti-epileptic Notes: The respective estimations of probability of being active or inactiv as well as the number of related bioactivepounds found in the PASS database for each  clomifene activity are shown. Figure . Effects of the-lactam derivative and ketotifen fumarate on IgE-induced-hex release from RBL cells. Antigen-induced-hex release and spontaneous-hex release. Sensitised cells were challenged with DNP-BSA m g mL , and the resulting-hex enzyme release was quantified. Each value represents meanfifiSEM of triplicate determinations;  pared with controls.

Downloaded by at March W.J. Andrioli Figure . Cytotoxicity of the-lactam derivative on RBL cells determined by MTT assay. The percentage of cell viability was calculated  Aloin relative to the untreated control. The cells were incubated with the-lactam derivative in CO . Effects of the-lactam derivative on-hex enzyme activity. Inhibition levels at 8 were equal to 8 and 4, respective indicating that the activity of the-lactam derivative is mainly due to its ability to inhibit degranulation. both used as reference drugs in this study. Azelastine and ketotifen have been recently classified as multiple action dru suggested tobine antihistamin mast cell stabilisation and anti-inflammatory effects . The mechanism by which both drugs inhibit mast cell activation remain unclear but one suspected mechanism is the blocking of IgE-regulated calcium channe stabilising the cell and preventing the release of histamine and related mediators .

In additi inhibition of intracellular Cafifielevation levels leads to the inhibition of  granisetron 107007-99-8 Cafi dependent P which is also critical for granule exocytosis . The effects of the-lactam derivative on the activity of-hex were also examined to clarify whether its effect was due to inhibition of enzyme activity or degranulation. As shown in Figure , the activepound weakly inhibits the enzyme activity of-h since 0 m M of the-lactam derivative causes only 4 enzyme inhibiti demonstrating that the reduction on quantified-h in the presence of the-lactam derivati is mostly attributable to the capacity of thepound to inhibit the secretion of-hex from the RBL cells. Furthermo the incubation of RBL cel in the presence of the-lactam derivativ for 4 h did not affect the cell viabili assessed using the-diphenyltetrazolium bromide cytotoxicity assay. As shown in Figure , only a small  buy PS-341 reduction in cell viability was observed after cell treatment with the highest drug concentration .

The inhibitory activity of the-lactam derivative against mast cell degranulation indicate that it is a promising candidate for the development of anti-allergic agent with the required action mechanism. Furthermo the in vitro cytotoxic concentration against RBL cells was much higher than the effective anti-allergic ones. Therefo the-lactam derivative seems to be safe for future applicatio but additional studies to certify both the acute and chronic  archaea toxicities of thispound are necessary Experimental . General experimental procedures H-and 3 C-NMR spectra were recorded in CD.