Antiplasmodial structure-activity relationship of 3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide derivatives

Derivatives of 3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide (4b-g, 5b-g, 6a-g) were synthesized and evaluated for their capacity to inhibit the growth of chloroquine-resistant Plasmodium falciparum FCB1 strain in culture. Compound 7-chloro-2-(2-furylcarbonyl)-3-trifluoromethyl-1,4-quinoxaline di-N-oxide (5g) was the most active being almost 5 times more active than chloroquine. It was also 50 times more active against P. falciparum than toxic toward MCF7 cells. Structural characteristics for a quinoxaline to be active were defined: bioisosteric modification of phenyl group by 2-thienyl or 2-furyl subunits, R2 position must be free or occupied by a methyl group and R1 position must be free or occupied by Cl, CH3, OCH3 or CF3.     

Gene expression in Plasmodium: from gametocytes to sporozoites

Completion of the complex developmental program of Plasmodium in the mosquito is essential for parasite transmission, yet this part of its life cycle is still poorly understood. In recent years, considerable progress has been made in the identification and characterization of genes expressed during parasite development in the mosquito. This line of investigation was greatly facilitated by the availability of the genome sequence of several Plasmodium, and by the application of approaches such as proteomics, microarrays, gene disruption by homologous recombination (gene knockout) and by use of subtraction libraries. Here, we review what is presently known about genes expressed in gametocytes and during the Plasmodium life cycle in the mosquito.     

Reproductive status of endemic felid species in Latin American zoos and implications for ex situ conservation

Reproductive evaluations were conducted on 185 male cats representing eight endemic Latin American species that were maintained in 44 zoos and private facilities in 12 Latin American countries. Reproductive assessments (testicular measures, ejaculate quality, and blood testosterone/cortisol concentration) were used to establish normative values for large‐ and small‐sized cats in Latin American collections. Data also were analyzed using multiple regression to study the impact of proven breeder status, diet, and various animal housing combinations. Most felids (>95%) in the survey were of wild‐born origin, and <20% had produced offspring in captivity. Larger felids had bigger testes and produced more semen, but tended to produce low‐sperm‐density ejaculates. The ejaculates of small felids were more sperm‐concentrated, but contained fewer total spermatozoa. Sperm motility was unrelated to species size, and certain species (puma, margay, tigrina, and jaguarundi) consistently produced few (<40%) normal sperm forms. Across species, >50% of males had low sperm counts (<1 million total sperm per ejaculate). Among large cats (jaguars and pumas), proven breeders had larger (P<0.05) testes, greater semen volume, and more normal sperm than nonbreeders. Males on adequate diets had higher (P<0.05) circulating cortisol. Among small‐sized felids, proven breeders had higher (P<0.05) testosterone, and males housed alone or paired with a conspecific female had more (P<0.05) total sperm per ejaculate and greater (P<0.05) seminal and testicular volumes. Fifty‐nine ejaculates (potentially representing ～100 artificial insemination (AI) or 26,000 in vitro fertilization (IVF) procedures) were cryopreserved for a felid genome resource bank. In conclusion, breeding success and reproductive traits for many endemic felids in Latin American zoos appear to be suboptimal, and likely would benefit from improvements in diet and exhibitry. Technology transfer and continued training of zoo staff and scientists in Latin American countries are essential if these zoos are to achieve their tremendous conservation potential for felids and other threatened endemic species. Zoo Biol 22:421–441, 2003. © 2003 Wiley‐Liss, Inc.     

The opposite effects of short- and long-term salt loading on pituitary adrenal axis activity in rats.

Osmotic stimulation has been shown to modify corticotropin responsiveness. We compared the effects of short- and long-term salt loading on pituitary-adrenal activity in control rats receiving tap water and rats submitted to salt loading for 1 day (S1) or 8 days (S8). Corticosterone (B) and adrenocorticotropic hormone (ACTH) plasma levels were determined at 8 a. m. under basal conditions or after immobilization stress for 15 min or corticotropin-releasing hormone (CRH) stimulation. S1 rats showed a similar ACTH response to immobilization, but an increased CRH response. In contrast, S8 rats showed blunted responses after immobilization or CRH stimulation. To evaluate the circadian variation of this inhibitory effect on the stress in the S8 group, immobilization was also performed at 8 p. m. Plasma ACTH and B levels under resting conditions were higher at 8 p. m. than 8 a. m. (p < 0.05) in control and S8 rats. The ACTH response to immobilization in the S8 group was lower than control at both 8 a. m. and 8 p. m. (p < 0.05); however, this reduction was more evident the morning, resulting in an inversion of the diurnal pattern with a higher ACTH response at 8 p. m. In conclusion, short osmotic stimulation results in an increased pituitary response to CRH, whereas prolonged stimulation decreases the pituitary response to CRH and immobilization, showing an interaction between osmoregulation and hypothalamus-pituitary-adrenocortical activity.     

Causal model to describe the variation of faecal coliform concentrations in a pilot-scale test consisting of ponds aligned in series

In this study, the application of path analysis was tested to validate a causal model developed to verify the influence on several factors of the variation of faecal coliform concentration in pilot-scale ponds that treat domestic wastewater under distinct physical and operational characteristics. The ponds, aligned in series, are located in the city of Campina Grande, Northeastern Brazil. The model proved to be efficient for describing the variation in both secondary facultative and maturation ponds. The coefficient of determination (R²) ranged between 0.66 and 0.84 for the facultative ponds and between 0.54 and 0.95 for the maturation ponds. Effluent faecal coliform concentration was negatively affected by solar radiation in shallow ponds and positively affected by influent faecal coliform concentration in deep ponds. Typically the effects related to phytoplankton photosynthetic activity were well characterized in all shallow maturation ponds. Faecal coliform concentration was negatively affected by pH in almost all the cases. This model is not suitable for anaerobic ponds.     

Decolorization of synthetic dyes by basidiomycetes isolated from woods of the Atlantic Forest (PE), Brazil

In this study, the biodegradability of synthetic dyes used in the textile industry by Basidiomycetes collected in woods of the Atlantic Forest of Pernambuco, Brazil, was evaluated. Among the fungi, the following species were identified: Caripia montagnei, Datronia caperata, Earliella scabrosa, Fomitopsis feei, Ganoderma stiptatum, Hexagonia hydnoides, Pleurotus ostreatus, Pycnoporus sanguineus and Trametes membranacea. Mycelium discs (2 cm2) of each fungal isolate were transferred to 30 ml of King medium supplemented with 0.05% m/v of each of the following dyes: methyl orange, bromophenol blue (BB), methylene blue, Congo red, phenol red (PR) and methyl green (MG). All these species showed potential to decolorize the tested dyes, with decolorization efficiency varying from 7.26 to 99.2%. H. hydnoides and T. membrancea were the only species able to degrade all dyes. BB was effectively metabolized by P. sanguineus (97.4%), H. hydnoides (95.6%), E. scabrosa (96.6%) and T. membranacea (99.2%). E. scabrosa stood out among the isolates in dyes decolorization, allowing for efficiencies >90% for MG, PR, and BB.     

Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design,synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition

A series of artemisinin–vinyl sulfone hybrid molecules with the potential to act in the parasite food vacuole via endoperoxide activation and falcipain inhibition was synthesized and screened for antiplasmodial activity and falcipain-2 inhibition. All conjugates were active against the Plasmodium falciparum W2 strain in the low nanomolar range and those containing the Leu-hPhe core inhibited falcipain-2 in low micromolar range.     

Anti-tumoral activity of imidazoquines,a new class of antimalarials derived from primaquine

The growth inhibitory activity of imidazoquines, antimalarial imidazolidin-4-ones derived from primaquine, on human cancer cell lines HT-29, Caco-2, and MCF-7 has been evaluated. Primaquine, N-dipeptidyl-primaquine derivatives, and other quinolines have been included in the study for comparison purposes. Primaquine and some of its derivatives were significantly active against the MCF-7 human breast cancer cell line, so these compounds might represent useful leads targeted at the development of novel specific agents against breast cancer. Conversely, all compounds were generally inactive against HT-29, with only one of the imidazoquines having IC₅₀ below 50 μM. Activities against the Caco-2 cell line were modest and did not follow any defined trend.