Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex

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

Produção de maracujazeiro-amarelo sob diferentes densidades de plantio

O adensamento de plantas em cultivos do maracujazeiro-amarelo é importante por propiciar maior rentabilidade em menor área. O objetivo deste trabalho foi avaliar o efeito de diferentes densidades de plantio na produção, qualidade dos frutos e rentabilidade do maracujazeiro-amarelo. O experimento foi instalado e conduzido em pomar comercial da Fazenda Sant'ana, Município de São Tiago, MG. O delineamento experimental utilizado foi o de blocos casualizados com cinco tratamentos e quatro repetições. Os tratamentos constituíram-se de diferentes espaçamentos na linha de plantio: T1, 1,0 m (3.330 plantas/ha); T2, 1,5 m (2.220 plantas/ha); T3, 2,0 m (1.660 plantas/ha); T4, 3,0 m (1.100 plantas/ha) e T5, 4,0 m (830 plantas/ha). O espaçamento entre linhas foi de 3,0 m em todos os tratamentos. Cada parcela foi constituída de 12 m de comprimento por 3,0 m de largura (36 m²). O plantio foi realizado em outubro de 2001, e a colheita, a partir de abril, estendendo-se até agosto de 2002. A maior produtividade foi estimada em 11,9 t/ha na densidade de 1.841 plantas/ha. O adensamento não altera a qualidade do fruto. A máxima eficiência econômica foi alcançada na densidade de 1.340 plantas/ha, com rentabilidade de R$ 1.321,92/ha

New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum

Background: The emergence and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy in Southeast Asia prompted the need to develop new endoperoxide-type drugs. Methods: A chemically diverse library of endoperoxides was designed and synthesized. The compounds were screened for in vitro and in vivo anti-malarial activity using, respectively, the SYBR Green I assay and a mouse model. Ring survival and mature stage survival assays were performed against artemisinin-resistant and artemisinin-sensitive P. falciparum strains. Cytotoxicity was evaluated against mammalian cell lines V79 and HepG2, using the MTT assay. Results: The synthesis and anti-malarial activity of 21 new endoperoxide-derived compounds is reported, where the peroxide pharmacophore is part of a trioxolane (ozonide) or a tetraoxane moiety, flanked by adamantane and a substituted cyclohexyl ring. Eight compounds exhibited sub-micromolar anti-malarial activity (IC50 0.3–71.1 nM), no cross-resistance with artemisinin or quinolone derivatives and negligible cytotoxicity towards mammalian cells. From these, six produced ring stage survival < 1% against the resistant strain IPC5202 and three of them totally suppressed Plasmodium berghei parasitaemia in mice after oral administration. Conclusion: The investigated, trioxolane–tetrazole conjugates LC131 and LC136 emerged as potential anti-malarial candidates; they show negligible toxicity towards mammalian cells, ability to kill intra-erythrocytic asexual stages of artemisinin-resistant P. falciparum and capacity to totally suppress P. berghei parasitaemia in mice.info:eu-repo/semantics/publishedVersio

Parâmetros genéticos e análise de trilha para o florescimento precoce e características agronômicas da alface

O objetivo deste trabalho foi avaliar os parâmetros genéticos das características agronômicas e de tolerância ao florescimento precoce de onze cultivares de alface, bem como verificar a existência de associação entre as características. O experimento foi realizado em ambiente protegido, em delineamento de blocos ao acaso, com quatro repetições e doze plantas por parcela. Quarenta e cinco dias após o transplantio das mudas, foram mensuradas as seguintes características: massa de matéria fresca total e "comercial" da parte aérea, massa de matéria seca "comercial" da parte aérea, massa de matéria fresca e seca da raiz, diâmetro e circunferência da cabeça, altura de planta, número de folhas por planta e número de dias até a antese. Há variabilidade genética entre as cultivares, em todas as variáveis, exceto quanto à circunferência de planta e matéria fresca da raiz. As cultivares Regina 500, Lívia e Atração foram superiores quanto ao número de dias para o florescimento e também para as demais características avaliadas. A seleção contra o florescimento precoce ocasionou ganho em todas as características; porém, não interferiu na matéria seca da raiz. A matéria fresca da parte aérea e o diâmetro de cabeça são indicadas para a seleção indireta contra o florescimento precoce

The Search for New Antimalarial Drugs from Plants Used to Treat Fever and Malaria or Plants Ramdomly Selected: a Review

In this review we discuss the ongoing situation of human malaria in the Brazilian Amazon, where it is endemic causing over 610,000 new acute cases yearly, a number which is on the increase. This is partly a result of drug resistant parasites and new antimalarial drugs are urgently needed. The approaches we have used in the search of new drugs during decades are now reviewed and include ethnopharmocology, plants randomly selected, extracts or isolated substances from plants shown to be active against the blood stage parasites in our previous studies. Emphasis is given on the medicinal plant Bidens pilosa   , proven to be active against the parasite blood stages in tests using freshly prepared plant extracts. The anti-sporozoite activity of one plant used in the Brazilian endemic area to prevent malaria is also described, the so called "Indian beer" (Ampelozizyphus amazonicus   , Rhamnaceae   ). Freshly prepared extracts from the roots of this plant were totally inactive against blood stage parasites, but active against sporozoites of Plasmodium gallinaceum   or the primary exoerythrocytic stages reducing tissue parasitism in inoculated chickens. This result will be of practical importance if confirmed in mammalian malaria. Problems and perspectives in the search for antimalarial drugs are discussed as well as the toxicological and clinical trials to validate some of the active plants for public health use in Brazil