Acyloxymethyl as a drug protecting group. Part 6: N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides as prodrugs of agents containing a secondary sulfonamide group

Tertiary N-acyloxymethyl- and N-[(aminocarbonyloxy)methyl]sulfonamides were synthesised and evaluated as novel classes of potential prodrugs of agents containing a secondary sulfonamide group. The chemical and plasma hydrolyses of the title compounds were studied by HPLC. Tertiary N-acyloxymethylsulfonamides are slowly and quantitatively hydrolysed to the parent sulfonamide in pH 7.4 phosphate buffer, with half-lives ranging from 20 h, for 7d, to 30 days, for 7g. Quantitative formation of the parent sulfonamide also occurs in human plasma, the half-lives being within 0.2-2.0 min for some substrates. The rapid rate of hydrolysis can be ascribed to plasma cholinesterase, as indicated by the complete inhibition observed at [eserine] = 0.10 mM. These results suggest that tertiary N-acyloxymethylsulfonamides are potentially useful prodrugs for agents containing a secondary sulfonamide group, especially with pKa < 8, combining a high stability in aqueous media with a high rate of plasma activation. In contrast, N-[(aminocarbonyloxy)methyl]sulfonamides 7h-j do not liberate the parent sulfonamide either in aqueous buffers or in human plasma and thus appear to be unsuitable for development as sulfonamide prodrugs.     

Characterization of a Rab11 homologue in Trypanosoma cruzi

Vesicle trafficking between organelles occurs through fusion of donor and specific acceptor membranes. This process is highly regulated and ensures proper direction in sorting and packaging of a number of molecules in eukaryotic cells. Monomeric GTPases of the Rab family play a pivotal role in the control of membrane fusion and vesicle traffic. In this paper, we characterize a Trypanosoma cruzi Rab 11 homologue (TcRab11) that shares at, the amino acid level, 40% similarity with human rab11, Arabdopsis thaliana rab11 and yeast rab11 homologue genes. Western blot analysis, using a polyclonal rabbit antiserum raised against a synthetic peptide derived from the COOH-terminus of predicted the TcRab11 protein, reacted to a 26kDa protein. In immunofluorescence assays, TcRab 11, was shown to be expressed in epimastigote and amastigote forms, but it was absent in trypomastigotes. Interestingly, the TcRab11 product seems to be located at the reservosome complex, a site of active endocytosis and vesicle fusion present only in the epimastigote stage. Therefore, TcRab11 may represent the first molecular marker of this peculiar organelle.     

Bi- and tetraflavonoids from Aristolochia ridicula

From stems of Aristolochia ridicula, two biflavones, four unusual chalcone-flavone dimers and one tetraflavonoid were isolated. The structures of the seven compounds were elucidated by spectroscopic methods.     

Influence of photoperiod on the uptake of nitrogen and phosphorus in the water by Eichhornia crassipes and Salvinia auriculata

The main goal of this research was to quantify the concentrations of total and ammonium N, nitrate, total and soluble P in the water in the presence of Eichhornia crassipes and Salvinia auriculata, which were submitted to two different photoperiods in a 24 hours incubation period in the laboratory. The macrophytes were incubated in plastic vials of approximately 1.5 litters, with a previously prepared solution with NH4NO3, NH4Cl, and KH2PO4. Eichhornia crassipes showed the highest average rate of reduction of all the nutrients analysed in relation to Salvinia auriculata. The largest photoperiod reflected in a higher average rate of reduction of nutrients, in both plants. Therefore, we may expect that in some periods of the year (e.g. summer), the aquatic macrophytes would show higher growth rates and higher rates of nitrogen and phosphorus absorption. These results are important for the implementation and management of wastewater treatment systems in tropical areas using aquatic macrophytes.     

Angiotensin-(1-7) modulates the ouabain-insensitive Na+-ATPase activity from basolateral membrane of the proximal tubule

Angiotensin-(1-7) (Ang-(1-7)) modulates the Na+-ATPase, but not the Na+,K+-ATPase activity present in pig kidney proximal tubules. The Na+-ATPase, insensitive to ouabain, but sensitive to furosemide, is stimulated by Ang-(1-7) (68% by 10(-9) M), in a dose-dependent manner. This effect is due to an increase in Vmax, while the apparent affinity of the enzyme for Na+ is not modified. Saralasin, a general angiotensin receptor antagonist, abolishes the stimulation, demonstrating that the Ang-(1-7) effect is mediated by receptor. The Ang-(1-7) stimulatory effect is not changed by either PD 123319, an AT2 receptor antagonist, or A779, an Ang-(1-7) receptor antagonist. On the other hand, increasing the concentration of the AT1 receptor antagonist losartan from 10(-11) to 10(-9) M, reverses the Ang(1-7) stimulation completely. A further increase to 10(-3) M losartan reverses the Na+-ATPase activity to a level similar to that obtained with Ang-(1-7) (10(-9) M) alone. The stimulatory effect of Ang-(1-7) at 10(-9) M is similar to the effect of angiotensin II (AG II) alone. However, when the two peptides are both present, Na+-ATPase activity is restored to control values. These data suggest that Ang-(1-7) selectively modulates the Na+-ATPase activity present in basolateral membranes of kidney proximal tubules through a losartan-sensitive receptor. This receptor is probably different from the receptor involved in the stimulation of the Na+-ATPase activity by angiotensin II.     

Fungus-growing ants (Hymenoptera: Formicidae) on Santa Catarina Island, Brazil: patterns of occurrence

A taxonomic survey on fungus-growing ants (Attini) was made at 14 beaches on Santa Catarina Island (SC), Brazil. The samplings were manual, in soil or litterfall, in the following habitats: sandy beach, herbaceous vegetation and shrubby vegetation. From 12 species of Attini (ten of Acromyrmex Mayr and two of Cyphomyrmex Mayr), the most frequent were Cyphomyrmex morschi Emery and Acromyrmex crassispinus Forel, collected, respectively, on eight and ten of the monitored beaches. Altogether, Sorensen's similarity coefficients were high (range: 0.59-0.80), in spite of the lower numbers of ant species on sandy beaches.     

Ecology of mosquitoes (Diptera: Culicidae) in areas of Serra do Mar State Park, State of São Paulo, Brazil. III. Daily biting rhythms and lunar cycle influence

The ecology of mosquito species (Diptera: Culicidae) was studied in areas of the Serra do Mar State Park, State of S?o Paulo, Brazil. The influence of the lunar cycle and the daily biting rhythms of mosquito populations were analyzed. Systematized biweekly human bait collections were made in a silvatic environment for 24 consecutive months (January 1991 to December 1992). A total of 20,591 specimens of adult mosquitoes belonging to 55 species were collected from 545 catches. Sabethini species were captured exclusively during daylight periods, with the exception of Trichoprosopon digitatum, while members of Anophelinae predominated during nocturnal hours. Members of the subfamily Culicinae that were collected primary during nocturnal periods included Culex nigripalpus, Coquillettidia chrysonotum and Cq. venezuelensis while daytime catches included Psorophora ferox and Ps. albipes. Others members of culicines mosquitoes that were collected during both day and night included: Aedes serratus, Ae. scapularis and Ae. fulvus. Lunar cycles did not appear to influence the daily biting rhythms of most mosquito species in the area, but larger numbers of mosquitoes were collected during the new moon. Ae. scapularis were captured mainly during the full moon.     

Diurnal variation of rates of denitrification and nitrogen fixation of periphyton associated with Oryza glumaepatula Steud in an Amazonian Lake

The rates of denitrification and biological nitrogen fixation of the periphyton communities associated with the culms and adventitious root of Oryza glumaepatula in Lake Batata, State of Pará, Brazilian Amazonia, were investigated over the course of 24 h. N₂O was not detected during the period, demonstrating that denitrification was not occurring. The low concentration of nitrate in the water column was indicated as the main factor limiting the denitrification process. The rates of biological nitrogen fixation (BNF) in culms were lowest at night and early morning, while the highest values were measured at 1200 h. BNF rates in periphyton associated with adventitious roots were lowest during the morning, while highest values were measured at 1600 h. The difference in the daily patterns of BNF rates in the periphyton of culms and roots of O. glumaepatula in the euphotic zone was attributed to defferences in the availability of organic carbon which supports this process. In the periphyton of the culms, the BNF process was carried out by heterocystous cyanobacteria, which was photoautotrophs. In the periphyton of the adventitious roots, BNF was carried out by periphytic bacteria, and is heterotrophically mediated. This revised version was published online in July 2006 with corrections to the Cover Date.