Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents

© Cambridge University Press 2016We report the pharmacological activity of organoruthenium complexes containing chloroquine (CQ) as a chelating ligand. The complexes displayed intraerythrocytic activity against CQ-sensitive 3D7 and CQ-resistant W2 strains of Plasmodium falciparum, with potency and selectivity indexes similar to those of CQ. Complexes displayed activity against all intraerythrocytic stages, but moderate activity against Plasmodium berghei liver stages. However, unlike CQ, organoruthenium complexes impaired gametocyte viability and exhibited fast parasiticidal activity against trophozoites for P. falciparum. This functional property results from the ability of complexes to quickly induce oxidative stress. The parasitaemia of P. berghei-infected mice was reduced by treatment with the complex. Our findings demonstrated that using chloroquine for the synthesis of organoruthenium complexes retains potency and selectivity while leading to an increase in the spectrum of action and parasite killing rate relative to CQ.This research was funded by FAPESB (grant PET0042/2013, Brazil) to M.B.P.S, FAPESP (grant 14/10516-7, Brazil) to A.A.B. and Fundação para a Ciência e Tecnologia (grant PTDC/SAU-MIC/117060/2010 Portugal) to M.P. A.A.B. and M.B.P.S. are recipients of senior fellowships by CNPq (Brazil)info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

DNA damage and primordial follicle activation after in vitro culture of sheep ovarian cortex in Morus nigra leaf extract

ABSTRACT: This study evaluated the effect of Morus nigra leaf extract, with or without supplementation, on morphology, activation and DNA damage of preantral follicles cultured within sheep ovarian tissue. Ovaries were collected and divided into fragments, being one fixed for histological and Terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) analysis (fresh control). The remaining fragments were cultured for 7 days in alpha minimum essential media (α-MEM) supplemented with bovine serum albumin (BSA), insulin, transferrin, selenium, glutamine, hypoxanthine and ascorbic acid (α-MEM+; control medium) or into medium composed of M. nigra extract without supplements (0.1; 0.2 or 0.4mg/mL) or supplemented with the same substances described above for α-MEM+ (MN 0.1+; 0.2+ or 0.4+mg/mL). Then, tissues were destined to histological and TUNEL analysis. The α-MEM+ treatment had more morphologically normal follicles than all M. nigra extract treatments. However, α-MEM+ treatment also showed signs of atresia because the percentage of TUNEL positive cells was similar in α-MEM+ and in 0.1mg/mL M. nigra without and with supplements. Moreover, a reduction in the primordial follicles and an increase in the growing ones were observed in all treatments, except 0.2mg/mL M. nigra. In conclusion, the follicles cultured at 0.1mg/mL M. nigra extract were in good condition and able to continue their development, as demonstrated by the same rates of DNA damage and follicular activation as the control medium

Chemical composition and antiparasitic activity of essential oils from leaves of <i>Guatteria friesiana</i> and <i>Guatteria pogonopus</i> (Annonaceae)

<p>Natural products represent a valuable source for discovery of antiparasitic agents. Here, we describe the antiparasitic activity from essential oils extracted from leaves of <i>Guatteria friesiana</i> (EOGF) and <i>Guatteria pogonopus</i> (EOGP) (Annonaceae). The essential oils were obtained by hydrodistillation and analyzed by GC/MS and GC-FID. The sesquiterpenes are more abundant in both essential oils. <i>G. friesiana</i> are dominated by β-eudesmol (51.9%), γ-eudesmol (18.9%) andα-eudesmol (12.6%). The major compounds identified for EOGP were spathulenol (24.8%), γ-amorphene (14.7%) and germacrene D (11.8%). The essential oils demonstrated potent trypanocidal and antimalarial activities with values of IC₅₀ lower than 41.3 μg/mL<i>.</i> EOGF also inhibits the proliferation of amastigotes. In addition, we identified significant ultrastructural alterations induced by the essential oils, especially in the cell membrane, Golgi complex, endoplasmatic reticulum and mitochondria. The results presented herein reinforce the potential of other members of this family for search of antiparasitic compounds.</p

Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent

Submitted by Éder Freyre ([email protected]) on 2017-02-13T13:10:12Z No. of bitstreams: 1 ve_Diogo_Moreira_etal_CPqGM_2014.pdf: 1053015 bytes, checksum: 283a95300677183e0f6d3a26fe6a040c (MD5)Approved for entry into archive by Éder Freyre ([email protected]) on 2017-02-13T16:20:17Z (GMT) No. of bitstreams: 1 ve_Diogo_Moreira_etal_CPqGM_2014.pdf: 1053015 bytes, checksum: 283a95300677183e0f6d3a26fe6a040c (MD5)Made available in DSpace on 2017-02-13T16:20:17Z (GMT). No. of bitstreams: 1 ve_Diogo_Moreira_etal_CPqGM_2014.pdf: 1053015 bytes, checksum: 283a95300677183e0f6d3a26fe6a040c (MD5) Previous issue date: 2015CNPq, FAPESB, FAPEAL e CAPES.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal da Paraíba. Laboratório de Tecnologia Farmacêutica. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Laboratório de Tecnologia Farmacêutica. João Pessoa, PB, Brasil.Universidade Federal Rural de Pernambuco. Departamento de Química. Recife, PE, Brasil.Universidade Federal Rural de Pernambuco. Departamento de Química. Recife, PE, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the β-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol