ABSTRACT
In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, Plasmodium has acquired multidrug resistance, including the emergence of P. falciparum strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of Plasmodium. The tested compound in the in vitro assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity in vitro against chloroquine-resistant P. falciparum W2 strain. The mice model of P. berghei ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of Anopheles aquasalis with P. vivax infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia in vitro, being considered a molecule with high antiplasmodial activity and low toxicity. The in vivo analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of P. berghei ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of P. vivax in A. aquasalis, leading to a decrease in the number of oocysts recovered from the mosquitoes' midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of P. vivax infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite.
Subject(s)
Antimalarials , Malaria, Falciparum , Malaria, Vivax , Plasmodium , Mice , Animals , Antimalarials/pharmacology , Primaquine/pharmacology , Primaquine/therapeutic use , Oocysts , Parasitemia/parasitology , Copper/pharmacology , Malaria, Falciparum/parasitology , Chloroquine/pharmacology , Plasmodium falciparumABSTRACT
Abstract The state of Rio Grande do Norte is considered a data gap for bat species records in Brazil. The state is also currently target of large economic projects with potential impacts on bats, especially wind farms and mining enterprises. In addition, Rio Grande do Norte has few conservation units in which there is no systematic study on bat fauna. The Nísia Floresta National Forest (NFNF), a federally protected area of 174 hectares, is located in the eastern coast of Rio Grande do Norte and corresponds to one of the last remnants of Atlantic Forest in the state, in its northernmost limits. A bat inventory was conducted in NFNF using mist nets set at ground level, from sunset to sunrise, from December 2011 to December 2012, totaling 25 sampling nights. We captured 1,379 bats belonging to four families and 16 species. Artibeus planirostris (Phyllostomidae) was the most frequently captured species (n = 685; 50%), followed by Myotis lavali (Vespertilionidae) (n = 248; 18%) and Phyllostomus discolor (Phyllostomidae) (n = 147; 11%). Peropteryx leucoptera, Phyllostomus discolor, Phyllostomus hastatus, Lophostoma brasiliense, Lasiurus blossevillii, Myotis lavali, and Promops nasutus are new records for Rio Grande do Norte, increasing the current number of bat species from 25 to 32 in this state. Further inventories, especially using acoustic surveys with bat detectors, might add more species to the NFNF bat list.
Resumo O estado do Rio Grande do Norte é considerado uma lacuna de informações sobre ocorrência de morcegos no Brasil. O estado também é atualmente alvo de grandes empreendimentos com potencial impacto sobre a quiropterofauna, especialmente no setor de energia eólica e mineração. Além disso, apresenta poucas unidades de conservação, e estas não possuem sua quiropterofauna estudada de maneira sistematizada. A Floresta Nacional de Nísia Floresta (FNNF), uma unidade de conservação federal de 174 hectares, localiza-se na costa leste do Rio Grande do Norte e corresponde a um dos últimos remanescentes de Mata Atlântica no estado e no limite norte do bioma. Foi realizado um inventário de morcegos na FNNF com a utilização de redes de neblina armadas no nível do solo, do por do sol ao amanhecer, de dezembro de 2011 a dezembro de 2012, totalizando 25 noites de amostragem. Nós capturamos 1379 morcegos pertencentes a quatro famílias e 16 espécies. Artibeus planirostris (Phyllostomidae) foi a espécie mais frequentemente capturada (n = 685; 50%), seguida por Myotis lavali (Vespertilionidae) (n = 248; 18%) e Phyllostomus discolor (Phyllostomidae) (n = 147; 11%). Peropteryx leucoptera, Phyllostomus discolor, Phyllostomus hastatus, Lophostoma brasiliense, Lasiurus blossevillii, Myotis lavali e Promops nasutus são novos registros para o Rio Grande do Norte, aumentando o número atual de espécies de morcegos no estado de 25 para 32. Inventários adicionais, especialmente utilizando amostragens acústicas com detectores de morcegos, tendem a acrescentar novas espécies à lista de morcegos da FNNF.
