1-[2-(4-methyl-7-coumarinyloxy)ethyl]-4-(5-{1-[2-(4-methyl-7-coumarinyloxy)ethyl]-1h-1, 2, 3-triazol-4-yl}pentyl)-1h-1, 2, 3-triazole

Nature often produces compounds with a high degree of symmetry to reduce structural information and complexity. Synthesis of identical twin drugs, through the linkage of two identical pharmacophoric entities, is a classical strategy to produce more potent and/or selective drugs. Herein, two units of the privileged core of the coumarin hymecromone were linked together using “click chemistry”. Synthesis of 1-[2-(4-Methyl-7-coumarinyloxy)ethyl]-4-(5-{1-[2-(4-methyl- 7-coumarinyloxy)ethyl]-1H-1, 2, 3-triazol-4-yl}pentyl)-1H-1, 2, 3-triazole was achieved by coupling of two identical units of an azido coumarin with a symmetrical alkine using copper(I)-catalyzed alkyne-azide cycloaddition reaction, in good yields and with complete regioselectivity. © 2016 by the authors; licensee MDPI, Basel, Switzerland.2016

Evaluation of antibacterial and antioxidant activity of purple araçá essential oil (Psidium rufum, Myrtaceae)

ABSTRACT The aim of this study was to evaluate the antibacterial and antioxidant activities of essential oil (EO) from fresh leaves of Psidium rufum. The EO was extracted by hydrodistillation and identified by gas chromatography coupled to mass spectrometry. The antibacterial activity was evaluated by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Antioxidant activity was determined by β-carotene/linoleic acid co-oxidation system, 2,2-diphenyl-1-picrylhydrazyl radical scavenging and iron reduction methods. Hydrocarbon sesquiterpenes were the predominant class, indicating 1,8 cineole, α-longipinene as major. The EO was tested against the bacteria Staphylococcus aureus and Pseudomonas aeruginosa (MIC = 2,500 µg/mL and MBC = 20,000 µg/mL); Enterococcus faecalis (MIC = 2,500µg/mL and MBC > 20,000µg/mL) and Escherichia coli (MIC > 20,000µg/mL and MBC > 20,000µg/mL). The EO showed antioxidant potential due to β-carotene/linoleic acid co-oxidation system, with 76.63% of oxidation inhibition (1.0mg/mL) and due to the iron reduction power (5,38 μmol Fe 2+ /mg sample). The results are promising in recommending this species for the development of food, cosmetic and pharmaceutical products

Novel coumarins active against Trypanosoma cruzi and toxicity assessment using the animal model Caenorhabditis elegans

From 2nd Latin American Congress of Clinical and Laboratorial Toxicology Porto Alegre, Brazil. 3-6 June 2018Background: Chagas disease (CD) is a tropical parasitic disease. Although the number of people infected is very high, the only drugs available to treat CD, nifurtimox (Nfx) and benznidazole, are highly toxic, particularly in the chronic stage of the disease. Coumarins are a large class of compounds that display a wide range of interesting biological properties, such as antiparasitic. Hence, the aim of this work is to find a good antitrypanosomal drug with less toxicity. The use of simple organism models has become increasingly attractive for planning and simplifying efficient drug discovery. Within these models, Caenorhabditis elegans has emerged as a convenient and versatile tool with significant advantages for the toxicological potential identification for new compounds. Methods: Trypanocidal activity: Forty-two 4-methylamino-coumarins were assayed against the epimastigote form of Trypanosoma cruzi (Tulahuen 2 strain) by inhibitory concentration 50% (IC50). Toxicity assays: Lethal dose 50% (LD50) and Body Area were determined by Caenorhabditis elegans N2 strain (wild type) after acute exposure. Structure-activity relationship: A classificatory model was built using 3D descriptors. Results: Two of these coumarins demonstrated near equipotency to Nifurtimox (IC50 = 5.0 ± 1 μM), with values of: 11 h (LaSOM 266), (IC50 = 6.4 ± 1 μM) and 11 g (LaSOM 231), (IC50 = 8.2 ± 2.3 μM). In C. elegans it was possible to observe that Nfx showed greater toxicity in both the LD50 assay and the evaluation of the development of worms. It is possible to observe that the efficacy between Nfx and the synthesized compounds (11 h and 11 g) are similar. On the other hand, the toxicity of Nfx is approximately three times higher than that of the compounds. Results from the QSAR-3D study indicate that the volume and hydrophobicity of the substituents have a significant impact on the trypanocidal activities for derivatives that cause more than 50% of inhibition. These results show that the C. elegans model is efficient for screening potentially toxic compounds. Conclusion: Two coumarins (11 h and 11 g) showed activity against T. cruzi epimastigote similar to Nifurtimox, however with lower toxicity in both LD50 and development of C. elegans assays. These two compounds may be a feasible starting point for the development of new trypanocidal drugs

Efeito do alumínio sobre a absorção, o acúmulo e o fracionamento do fósforo em sorgo

O trabalho teve como objetivo estudar o efeito do Al sobre a absorção, o acúmulo e o fracionamento do P em duas cultivares de sorgo. As plantas foram expostas a níveis tóxicos de Al durante dez dias e, então, colhidas e determinados o crescimento em tamanho e produção de massa seca, os teores de Al e de P total e as diversas formas de P nas duas partes das plantas. Avaliou-se, também, o efeito do Al sobre a absorção de P pelas raízes de plantas intactas. O Al reduziu o crescimento da raiz seminal e a produção de matéria seca de raízes e parte aérea nas duas cultivares, especialmente na sensível. Os teores de Al e de P total aumentaram nas raízes, mas não foram modificados na parte aérea nas duas cultivares. A absorção de P, entretanto, decresceu na presença de Al nas duas cultivares, principalmente na sensível. O Al, de modo geral, modificou as concentrações das várias formas de P solúvel (Pi e Porg) e insolúvel (P RNA e Presidual), exceto a da forma P LIP. Algumas dessas modificações parecem ser importantes e podem estar relacionadas com o mecanismo de tolerância ao Al em sorgo.The objective of this work was to evaluate Al effect on uptake, accumulation and fractionation of P in two sorghum cultivars. Plants were treated with toxic levels of Al during ten days and then they were harvested and growth, dry matter yield, Al and total P contents and concentrations of the various P forms in the two parts of the plants were determined. Aluminum effect on P uptake was also evaluated in intact plants. Aluminum reduced the growth of the seminal root and dry matter yield in roots and tops of both cultivars, especially in the sensitive one. Aluminum and P contents increased in roots but did not change in the top of both cultivars. Phosphate uptake by roots, however, decreased in the presence of Al in both cultivars, especially in the sensitive one. Aluminum, in general, changed concentrations of all soluble (Pi e Porg) and insoluble P forms (P RNA e Presidual), except of the P LIP form. Some of these modifications seem to be important and may be related to Al tolerance mechanism in sorghum

Seeds of Amazonian Fabaceae as a source of new lectins

Seeds from fifty native Amazonian Fabaceae species (representing subfamilies Caesalpinioideae, Mimosoideae and Faboideae) were screened for the presence of new lectins. Their crude protein extracts were assayed for hemagglutinating activity (HA). The protein fractions of Anadenanthera peregrina, Dimorphandra caudata, Ormosia lignivalvis and Swartzia laevicarpa exhibited HA, and this activity was inhibited by galactose or lactose but not by glucose or mannose. The crude extract of S. laevicarpa exhibited HA activity only after ion exchange chromatography, and its lectin was further purified by affinity chromatography on immobilized lactose. Despite the large number of lectins that have been reported in leguminous plants, this is the first description of lectins in the genera Anadenanthera, Dimorphandra and Ormosia. The study of lectins from these genera and from Swartzia will contribute to the understanding of the evolutionary relationships of legume lectins in terms of their protein processing properties and structures