Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 µg/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1β, TNF-α, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile.

EOX showed in vitro and in vivo antitumour activity and low toxicity, which warrants further pharmacological studies.

Natural products have played a pivotal role for the discovery of anticancer drugs. Tonantzitlolones are flexibilan-type diterpenes rare in nature; therefore, few reports have shown antiviral and cytotoxic activities. This study aimed to investigate the in vivo antitumor action of Tonantzitlolone B (TNZ-B) and its toxicity. Toxicity was evaluated in mice (acute and micronucleus assays). Antitumor activity of TNZ-B (1.5 or 3 mg/kg intraperitoneally -i.p.) was assessed in Ehrlich ascites carcinoma model. Angiogenesis and reactive oxygen species (ROS) and nitric oxide (NO) production were also investigated, in addition to toxicological effects after 7-day treatment. The LD 50 (lethal dose 50%) was estimated at around 25 mg/kg (i.p.), and no genotoxicity was recorded. TNZ-B reduced the Ehrlich tumor's volume and total viable cancer cell count (p < 0.001 for both). Additionally, TNZ-B reduced peritumoral microvessel density (p < 0.01), suggesting antiangiogenic action. Moreover, a decrease was observed on ROS (p < 0.05) and nitric oxide (p < 0.001) levels. No significant clinical findings were observed in the analysis of biochemical, hematological, and histological (liver and kidney) parameters. In conclusion, TNZ-B exerts antitumor and antiangiogenic effects by reducing ROS and NO levels and has weak in vivo dose-repeated toxicity. These data contribute to elucidate the antitumor action of TNZ-B and point the way for further studies with this natural compound as an anticancer drug.

No abstract

O objetivo deste trabalho foi avaliar a evolução e o panorama atual das Unidades de Conservação (UCs) do Brasil, com enfoque na mesorregião Norte e Noroeste do Estado do Rio de Janeiro. A pesquisa foi realizada a partir de dados disponibilizados pelo Ministério do Meio Ambiente, como a distribuição das UCs no território, processada por Sistema de Informação Geográfico, informações sobre sua área, data de criação, tipologias e gestão. A receita obtida pelo ICMS ecológico foi analisada no sítio do CEPERJ. A primeira UC criada nessa mesoregião foi o Parque Estadual do Desengano, em 1970. A partir da década de 1990 houve aumento significativo de UCs e atualmente existem 40, sendo 27 de Uso Sustentável, representadas, principalmente, pela categoria Reserva Particular do Patrimônio Natural. Na categoria Proteção Integral, os parques compõem a maior parte das UCs. A Região Noroeste tem 4% de sua área total protegida por UCs, enquanto que na Região Norte Fluminense este percentual é de 6%. A presença de UCs tem auxiliado os municípios das regiões Norte e Noroeste quanto a captação do ICMS ecológico, totalizando cerca de R$ 86 milhões desde 2009, o que é pouco representativo em relação aos outros municípios do estado do Rio de Janeiro. A Mata Atlântica presente nestes territórios é diversificada, com diferentes fitofisionomias, onde habitam espécies sob ameaça de extinção. A expansão da quantidade e uma boa gestão das UCs já existentes são meios para aumentar a arrecadação fiscal dos municípios e diminuir a fragilidade ambiental regional, fruto de uma ocupação desordenada do território. As UCs podem proporcionar serviços ambientais essenciais, como a diminuição das secas, enchentes e erosão do solo, problemas ambientais recorrentes nesta mesorregião.