Screening for new bioactive peptides in South American anurans has been pioneered in frogs of the genus Phyllomedusa. All frogs of this genus have venomous skin secretions, i.e., a complex mixture of bioactive peptides against potential predators and pathogens that presumably evolved in a scenario of predator-prey interaction and defense against microbial invasion. For every new anuran species studied new peptides are found, with homologies to hormones, neurotransmitters, antimicrobials, and several other peptides with unknown biological activity. From Vittorio Erspamer findings, this genus has been reported as a "treasure store" of bioactive peptides, and several groups focus their research on these species. From 1966 to 2009, more than 200 peptide sequences from different Phyllomedusa species were deposited in UniProt and other databases. During the last decade, the emergence of high-throughput molecular technologies involving de novo peptide sequencing via tandem mass spectrometry, cDNA cloning, pharmacological screening, and surface plasmon resonance applied to peptide discovery, led to fast structural data acquisition and the generation of peptide molecular libraries. Research groups on bioactive peptides in Brazil using these new technologies, accounted for the exponential increase of new molecules described in the last decade, much higher than in any previous decades. Recently, these secretions were also reported as a rich source of multiple antimicrobial peptides effective against multidrug resistant strains of bacteria, fungi, protozoa, and virus, providing instructive lessons for the development of new and more efficient nanotechnological-based therapies for infectious diseases treatment. Therefore, novel drugs arising from the identification and analysis of bioactive peptides from South American anuran biodiversity have a promising future role on nanobiotechnology.

BackgroundMost hematophagous insects use host odours as chemical cues. The odour components, some physiological parameters and host attractiveness are affected by several conditions, including infection by parasites, e.g., plasmodia and, therefore, change the epidemiological scenario. This study evaluated the attractiveness of individuals with vivax malaria before, during (7 days) and after treatment (14 days) with specific antimalarial drugs.FindingsMosquito attractiveness to vivax-infected patients was assessed using a vertical olfactometer using the foot as a source of body odour. The ratio of Anopheles darlingi mosquitoes in the lower chamber of the olfactometer was used to calculate the attractiveness, and patient temperature was measured using a digital thermometer. An increased attractiveness was found only in patients bearing vivax gametocytes during the first experiment (early infection) (P < 0.001). Patients in the first experiment tended to have a higher body temperature, but grouping patients into fever and non-fever resulted in a higher attractiveness only in the fever group of gametocyte carriers, suggesting a synergistic effect of temperature and gametocytes in the host attractiveness to A. darlingi.ConclusionsGametocyte presence and fever in vivax malaria patients increased short distance host attractiveness to An. darlingi.

The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19th and 20th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate) values. Main results: (i) malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii) asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii) vivax malaria relapses were responsible for 30% of clinical cases; (iv) malaria risk for the residents was evaluated as 20–25% for vivax and 5–7% for falciparum malaria; (v) anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi) very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by the Hydroelectric Power Plants constructions.

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O presente trabalho descreve a atividade do extrato etanólico (EE) dos frutos de Combretum leprosum, do triterpeno 3b, 6b, 16b-triidroxilup-20(29)-eno (1) e seus derivados sintéticos (1a-1d), sobre promastigotas de Leishmania amazonensis. O EE apresentou atividade leishmanicida e o valor de IC 50 foi de 24,8 mg mL -1 . Já o triterpeno 3b, 6b, 16b-trihidroxilup-20(29)-eno (1), na concentração de 5,0 mg mL -1 , apresentou uma potente ação inibitória sobre a proliferação das promastigotas (IC 50 = 3,3 mg mL -1 ). Entre os derivados sintéticos, apenas 1b e 1d apresentaram atividade contra as promastigotas (IC 50 = 3,48 mg mL -1 e 5,8 mg mL -1 , respectivamente). Por outro lado, o derivado sintético 1a não apresentou atividade sobre as promastigotas de L. amazonensis. O EE, (1) e os derivados sintéticos 1a-1d não apresentaram efeito citotóxico sobre macrófagos peritoneais de camundongos. Estes resultados fornecem evidencias de que o extrato etanólico e o lupano isolado de C. leprosum possui atividade contra promastigotas de L. amazonensis, podendo ser utilizados como ferramentas no estudo de novas drogas leishmanicidas. This paper describes the activity of the ethanolic extract (EE), obtained from the fruits of Combretum leprosum, the triterpene 3b, 6b, 16b-trihydroxylup-20(29)-ene (1) and its synthetic derivatives 1a-1d on Leishmania amazonensis promastigotes. The EE displayed leishmanicidal activity and the IC 50 was 24.8 mg mL -1 . However, the triterpene 3b, 6b, 16b-trihydroxylup-20(29)-ene (1), at a concentration of 5.0 mg mL -1 , showed a potent inhibitory activity on promastigotes proliferation (IC 50 = 3.3 mg mL -1 ). Among the synthetic derivatives, only (1b) and (1d) were active against promastigotes (IC 50 = 3.48 mg mL -1 and 5.8 mg mL -1 , respectively). Moreover, the synthetic derivative 1a showed no activity on promastigotes of L. amazonensis. EE, (1) and the synthetic derivatives 1a-1d showed no cytotoxic effect on mice peritoneal macrophages. These results provide evidence that the ethanolic extract and the lupane isolated from C. leprosum was active against promastigotes of L. amazonensis, and may be used as a tool in the studies of new antileishmanial drugs. The clinical manifestations of leishmaniasis are often divided in cutaneous, diffuse cutaneous, mucocutaneous and visceral leishmaniasis. Keywords3,4 Cutaneous leishmaniasis can Teles et al. 937 Vol. 22, No. 5, 2011 be spontaneously healed after a few months, or, depending on the Leishmania species, develop into diffuse cutaneous, relapsing cutaneous or mucocutaneous leishmaniasis. Visceral leishmaniasis, if untreated, leads to death in most patients. 5,6 This disease causes considerable morbidity and severe face-disfigurement lesions on the affected people.Nowadays, chemotherapy for leishmaniasis is still based on pentavalent antimonials (Glucantime and Pentostam), diamines (Pentamidine) and antifungal polyene (Amphotericin B). These are only a few of the drugs available since 1940. Unfortunately, they are generally toxic, expensive, s...

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Rev. Virtual Quim. |Vol 4| |No. 6| |692-702| 692 Artigo In Vitro Atileishmanial and Cytotoxic Activities of Annona mucosa (Annonaceae) de Lima, J. P. S.; Pinheiro, M. L. B.;* Santos, A. M. G.; Pereira, J. L. S.; Santos, D. M. F.; Barison, A.; Silva-Jardim, I.; Costa, E. V.Rev. Virtual Quim., 2012, 4 (6), 692-702. Data de publicação na Web: 11 de novembro de 2012 Resumo: A atividade antileishmania dos extratos das folhas e sementes de Annona mucosa, e do alcaloide oxoaporfínico liriodenina isolado do extrato diclorometano das folhas foi avaliada in vitro contra formas promastigotas de três espécies de Leishmania, e formas amastigotas intracelulares de Leishmania amazonensis. A atividade citotóxica foi avaliada contra macrófagos peritoneais de camundongos. O extrato diclorometano das folhas foi o mais ativo contra Leshmania spp. apresentando valores de CI 50 menores que 30 µg.mL -1. O alcaloide liriodenina foi o mais citotóxico contra macrófagos peritoneais. Os extratos hexânicos das sementes apresentaram maior indice de seletividade contra Leishmania spp. (IS = 5,93 a 1,54). Todas as amostras foram ativas contra formas amastigotas intracelulares, inibindo, depois de 96h, mais que 70% da replicação de amastigotas nos macrófagos infectados. A investigação fitoquímica do extrato diclorometano das folhas de A. mucosa levou ao isolamento dos alcaloides oxoaporfínicos atherospermidina (1) e liriodenina (2), identificados com base nos seus dados espectroscópicos, principalmente RMN 1D/2D, e comparação com os dados da literatura. AbstractsThe antileishmanial activity of extracts from the leaves and seeds of Annona mucosa, and of the oxoaporphine alkaloid liriodenine isolated from the dichloromethane extract of the leaves, were evaluated in vitro against promastigote forms of three Leishmania species and against intracellular amastigote forms of L. amazonensis. Cytotoxic activity was evaluated against peritoneal macrophages of mice. The dichloromethane extract from the leaves was the most active against Leishmania spp., showing IC 50 values lower than 30 µg.mL -1 . Liriodenine was the most cytotoxic against peritoneal macrophages. Hexane extracts of seeds showed the highest selectivity index against Leishmania spp. (SI = 5.93 to 1.54). All samples were active against intracellular amastigote forms, after 96 h inhibiting more than 70% of amastigote replication in infected macrophages. Phytochemical investigation of the dichloromethane extract from the leaves of A. mucosa led to the isolation of the oxoaporphine alkaloids atherospermidine (1) and liriodenine (2), identified on the basis of their spectroscopic data, mainly 1D/2D NMR, and comparison with literature data.