Chagas disease affects more than 10 million people worldwide, and yet, as it has historically been known as a disease of the poor, it remains highly neglected. Two currently available drugs exhibit severe toxicity and low effectiveness, especially in the chronic phase, while new drug discovery has been halted for years as a result of a lack of interest from pharmaceutical companies. Although attempts to repurpose the antifungal drugs posaconazole and ravuconazole (inhibitors of fungal sterol 14␣-demethylase [CYP51]) are finally in progress, development of cheaper and more efficient, preferably Trypanosoma cruzi-specific, chemotherapies would be highly advantageous. We have recently reported that the experimental T. cruzi CYP51 inhibitor VNI cures with 100% survival and 100% parasitological clearance both acute and chronic murine infections with the Tulahuen strain of T. cruzi. In this work, we further explored the potential of VNI by assaying nitro-derivative-resistant T. cruzi strains, Y and Colombiana, in highly stringent protocols of acute infection. The data show high antiparasitic efficacy of VNI and its derivative (VNI/VNF) against both forms of T. cruzi that are relevant for mammalian host infection (bloodstream and amastigotes), with the in vivo potency, at 25 mg/kg twice a day (b.i.d.), similar to that of benznidazole (100 mg/kg/day). Transmission electron microscopy and reverse mutation tests were performed to explore cellular ultrastructural and mutagenic aspects of VNI, respectively. No mutagenic potential could be seen by the Ames test at up to 3.5 M, and the main ultrastructural damage induced by VNI in T. cruzi was related to Golgi apparatus and endoplasmic reticulum organization, with membrane blebs presenting an autophagic phenotype. Thus, these preliminary studies confirm VNI as a very promising trypanocidal drug candidate for Chagas disease therapy. Chagas disease (CD), a neglected lifelong malady caused by the intracellular protozoan parasite Trypanosoma cruzi, is a notorious health problem in Latin America and an emerging global health issue, mainly due to immigration of infected individuals to other continents (primarily to North America and Europe) but also because of broadening of the insect vector distribution areas (1). No vaccine is available, and the current therapy for the infection (nifurtimox [Nf] and benznidazole [Bz]) is largely insufficient, having undesirable side effects and limited efficacy especially in the later chronic stages (2). However, novel compounds for CD do not attract the investment of most pharmaceutical companies, especially due to large costs versus low economic profits, exposing the importance of academic research and technological development support for drug design and development of new leads and hits for this as well as other neglected parasitic illnesses that afflict millions of the poorest people worldwide. In this vein, for over 3 decades inhibitors of sterol biosynthesis have been considered potential antichagasic agents (3-6), because, similar to the...

The concentration 0.2 μg/μL of M. oleifera seed extract recommended to treat water for humans did not pose a risk to human health. The mutagenicity detected at concentrations higher than 0.4 μg/μL was not due to WSMoL, lectin isolated from extract.

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Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide.

Superfruits have a high nutritional value due to their richness in nutrients, antioxidants, proven or potential health benefits and taste appeal. However, there are no scientific criteria for defining which fruits are superfruits. In Brazil, several palms have an edible palm heart, the best known and most widely appreciated of which is called Acai (Euterpe oleracea). Euterpe edulis Mart., commonly called jussara, is an evergreen species that grows in the rainforest. Having initially been consumed in the form of juice and pulp, they have since been incorporated as an ingredient in many foods. A risk assessment to identify adverse health effects is a prerequisite for taking forward the development of new drugs, cosmetics and foods. To make a toxicological evaluation of E. edulis, in the present work this prerequisite was met by an interdisciplinary network that performed mass spectroscopy analyses, blood biochemistry, genotoxicity, bacterial reverse mutation and cytotoxicity assays. Positive mutagenicity results were detected for Salmonella typhimurium TA97 at low doses, and positive results were also obtained for the mammalian erythrocyte micronucleus assay, indicating that the pulp of E. edulis contains compounds with the capacity to induce mutagenicity and clastogenic/aneugenic effects.

ABSTRACT. Risk assessment can provide a comprehensive estimate of potential effects of contaminants under specific, well-defined, and well-described circumstances, providing quantitative relationships between exposure and effects to identify and to define areas of concern. We investigated the mutagenic activity of particulate matter in air samples collected from three sites in Rio de Janeiro city. Samples were collected using a high-volume sampler at Avenida Brasil, at Campus of Universidade do Estado do Rio de Janeiro, and at Rebouças Tunnel. Six polycyclic aromatic hydrocarbons were quantified by gas chromatography/mass spectrometry. Salmonella typhimurium TA98 and the derivative strains TA98/1.8-DNP 6 , YG1021, and YG1024, Health risk in urban airborne in Rio de Janeiro commonly used in mutagenicity assays, were treated (10-50 µg/plate), with and without exogenous metabolization. The highest values for the polycyclic aromatic hydrocarbons were detected at Rebouças Tunnel. For chrysene, as an example, the concentration was nearly 200 times higher than that established by the US Environmental Protection Agency. Frequent traffic jams can place bus drivers who go through the Rebouças Tunnel at risk of exposure to up to 0.69 ng/m 3 benzo(a) pyrene. Independent of exogenous metabolization, mutagenicity was detected in strains YG1021 and YG1024 at all the sites, suggesting nitro and amino derivatives of polycyclic aromatic hydrocarbons. Rebouças Tunnel air samples gave the highest values for rev/µg and rev/m 3 . This could be due to the fact that the long, enclosed passageway through a mountain restricts ventilation. The cancer risk estimate in this study was 10 -3 for the benzo(a)pyrene, at the two sites, indicating a high risk.

f Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.

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