Lignans and neolignans as lead compounds

Many lignans and neolignans have served as lead compounds for the development of new drugs. Perhaps the best known example is podophyllotoxin, an antimitotic compound that binds to tubulin. Etoposide and teniposide are derived from podophyllotoxin, but their antitumoural activity is due to inhibition of topoisomerase II. Combination of both pharmacophores has led to compounds with a dual mechanism of action, such as azatoxin. Dihydrobenzofuran neolignans, based on the natural lead 3,4-di-O-methylcedrusin, have also been investigated as potential antitumoural agents; the dimerisation product of caffeic acid methyl ester was the most active compound. Here too, he cytotoxic activity was due to inhibition of tubulin polymerisation. In addition, the same compounds showed antiangiogenic activity. Podophyllotoxin, as well as other types of lignans, such as dibenzylbutyrolactones related to arctigenin, dibenzocyclooctadiene-type lignans, and dibenzylbutanes, have been explored as leads for antiviral agents (also including HIV). Synthetic 8.O.4-neolignans have been evaluated for their antileishmanial and antifungal properties. Detailed study of the antifungal properties of the phenylpropanoid moieties has resulted in the design of highly active arylpropanoid derivatives. Other examples where lignans have been used as lead compounds include enzyme inhibitors of phosphodiesterase IV and V, and 5-lipoxygenase, and for the development of hypolipidemic and antirheumatic agents.     

Electronic structure calculations as a tool for investigating acyl migrations in ester saponins

The possibility of acyl migrations in ester saponins from Maesa lanceolata was investigated by molecular mechanics and electronic structure calculations carried out on the major constituent maesasaponin IV3 (3beta-O-[[alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-galactopyranosyl-(1-->3)]-[beta-D-galactopyranosyl-(1-->2)]-beta-D-gluco-pyranuronyl]-21beta-angeloyloxy-22alpha-propanoyloxy-13beta,28-oxido-olean-16alpha, 28alpha-diol). It was confirmed that acyl migrations could occur in rings D and E of maesasaponins.     

Positive effect of taurine on preimplantation development of mouse embryos in vitro.

The effect of various taurine concentrations in modified Tyrode's medium on in vitro fertilization of mouse oocytes was examined. No significant difference in fertilization rate was found at concentrations of 0, 0.1, 1, 5, 10 and 20 mM taurine. In a second series of experiments, the effect of taurine on preimplantation embryonic development after fertilization in vitro was studied. At concentrations of 1, 5, 10 and 20 mM taurine, significantly more two-cell embryos reached the blastocyst stage compared with medium without taurine. Culture in the presence of 5 mM or 10 mM taurine resulted in blastocysts with the highest mean number of cells. The positive effect of taurine on embryonic development was found to be more pronounced both in a second medium (human tubal fluid medium) which has a higher potassium concentration than Tyrode's medium, and in a modified Tyrode's medium with an increased potassium concentration. In addition to these in vitro studies, it is reported that taurine comprised about 59% of the total free amino acid content in mouse oviduct flushings, compared with 17% in mouse serum.     

Mutagenicity of pyrrolizidine alkaloids in the Salmonella typhimurium/mammalian microsome system.

The mutagenicity of a series of pyrrolizidine alkaloids, and of extracts from several Italian Senecio species containing pyrrolizidine alkaloids, including S. inaequidens, S. fuchsii and S. cacaliaster, were tested using the Salmonella typhimurium/mammalian microsome system. Retrorsine, senecivernine, seneciphylline and the Senecio extracts showed a weakly mutagenic activity.     

Multi‐male captive groups of endangered dama gazelle: Social rank,aggression, and enclosure effects

A study carried out in four multi‐male groups of captive dama gazelle (Gazella dama mhorr) characterized the social rank order of males and possible enclosure effects on aggression rate. A strong relationship between rank and age was found. The results also showed that dominant individuals in the two smallest enclosures were more aggressive than their herdmates, suggesting a more stressful environment, which might precipitate unstable or challenged hierarchies when the animals live in a more restricted enclosure. Subordinate males performed submissive responses at a higher frequency, irrespective of the size of the enclosure. The frequency of interactions between the gazelles, on the other hand, was affected by enclosure size, since high‐ranking males showed higher values than low‐ranking males in the two smallest enclosures. Frequencies of aggressive acts, retreats, and related interactions were similar in all the herds. Implications for the management of the species in captivity are discussed. Zoo Biol 19:121–129, 2000. © 2000 Wiley‐Liss, Inc.     

Differential post-translational modification of CD63 molecules during maturation of human dendritic cells.

The capacity of dendritic cells to initiate T cell responses is related to their ability to redistribute MHC class II molecules from the intracellular MHC class II compartments to the cell surface. This redistribution occurs during dendritic cell development as they are converted from an antigen capturing, immature dendritic cell into an MHC class II-peptide presenting mature dendritic cell. During this maturation, antigen uptake and processing are down-regulated and peptide-loaded class II complexes become expressed in a stable manner on the cell surface. Here we report that the tetraspanin CD63, that associates with intracellularly localized MHC class II molecules in immature dendritic cells, was modified post-translationally by poly N-acetyl lactosamine addition during maturation. This modification of CD63 was accompanied by a change in morphology of MHC class II compartments from typical multivesicular organelles to structures containing densely packed lipid moieties. Post-translational modification of CD63 may be involved in the functional and morphological changes of MHC class II compartments that occur during dendritic cell maturation.     

Photosynthesis in Plants of Four Tropical Species Growing under Elevated CO2

We studied the responses of leaf gas exchange and growth to an increase in atmospheric CO₂ concentration in four tropical deciduous species differing in carbon fixation metabolism: Alternanthera crucis, C3-C4; Ipomoea carnea, C3; Jatropha gossypifolia, C3; and Talinum triangulare, inducible-CAM. In the first stage, plants were grown in one open-top chamber at a CO₂ concentration of 560±40 mol mol^-1 (EC), one ambient CO₂ concentration chamber (AC), and one unenclosed plot (U). In the second stage, plants were grown in five EC chambers (CO₂ concentration = 680±30 mol mol^-1), five AC chambers, and five unenclosed plots. During the first weeks under EC in the first stage, plants of all the species had a very marked increase in their maximal net photosynthetic rates (P _max) of 3.5 times on average; this stimulatory effect was maintained for 11-15 weeks, rates dampening afterward to values still higher than controls for 37 weeks. After a suspension of CO₂ enrichment for 6 weeks, an increase in P _max of EC plants over the controls was found in plants of all the species until week 82 of the experiment. Stomatal conductance (g) showed no response to EC. Carboxylation efficiency decreased in all the species under EC