Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity

The aim of this study was to identify a candidate drug for the development of anti-tuberculosis therapy from previously synthesized compounds based on the thiosemicarbazones, semicarbazones, dithio-carbazates and hydrazide/hydrazones compounds. The minimal inhibitory concentration (MIC) of these compounds against Mycobacterium tuberculosis was determined. Their in vitro cytotoxicity to J774 cells (IC(50)) was determined to establish a selectivity index (SI) (SI = IC(50)/MIC). The best compounds were the thiosemicarbazones (2, 3 and 4) and the hydrazide/hydrazones (14, 15, 16 and 18). The results are comparable to or better than those of ""first line"" or ""second line"" drugs commonly used to treat TB, suggesting these compounds as anti-TB drug candidates. (C) 2010 Elsevier Masson SAS. All rights reserved.

Licença compulsória para medicamentos como política pública: o caso do anti-retroviral efavirenz

O objetivo deste estudo é avaliar o processo de implementação da Licença Compulsória no caso do anti-retroviral efavirenz. Esta pesquisa é de caráter descritivo, o meio de investigação foi o estudo de caso e foi conduzido com entrevistas semi-estruturadas contendo questões abertas para um conjunto de atores representativos da área da Saúde Pública que participaram do processo da licença compulsória residentes nos estados do Rio de Janeiro e São Paulo e no Distrito Federal durante os meses de outubro a dezembro de 2009. Permitiu-se que esses indivíduos se expressassem mais ou menos livremente de forma que eles produzissem discursos. Para a análise dos discursos, utilizou-se a técnica do Discurso do Sujeito Coletivo (DSC). Os resultados demonstraram que o Brasil possui capacitação tecnológica para desenvolver e produzir anti-retrovirais em um prazo relativamente curto. Os resultados mostram ainda que a Licença Compulsória ajudou a refrear os gastos com anti-retrovirais e que o instrumento pode ser utilizado para garantir o acesso da população a medicamentos anti-retrovirais de alto custo e estratégicos para o Sistema Único de Saúde em um ambiente de recursos limitados sempre que se chegar a um impasse na negociação para redução de preços com os laboratórios farmacêuticos transnacionais.

Avaliação das atividades anti-toxoplásmica, antioxidante e antiinflamatória dos monoterpenos timol (lippia sidoides) e estragol (croton zenhtneri)

Toxoplasmosis, a benign disease in normal healthy individuals, can have serious effects in pregnant women and immunocompromised patients. It is a parasitic disease caused by Toxoplasma gondii (Tg), an obligatory intracellular protozoan. The prophylactic and therapeutic arsenal against this parasite is very restricted. Thus, there is an ongoing search for novel drugs and therapeutic strategies. A promising alternative is a rational approach using medicinal plants. This study aimed to standardize methodologies for assessing the toxicological, antiproliferative, antioxidant, antiinflammatory and anti-Toxoplasma effects of Estragole and Thymol compounds isolated from species of plants (Lippia sidoides and Croton zenhtneri) commonly used in the Cariri region of Ceara State, Brazil. First we evaluated in vivo toxicity and conducted a pathological analysis of mice livers. In vivo antiinflammatory activity was assessed using air pouch and paw edema methods. Cytotoxicity assays were performed and antiproliferative, antioxidant and nitric oxide production analyzed. Anti-Toxoplasma activity was evaluated in a congenital experimental model with varying stages of maternal infection using the ME-49 strain and a non- congenital model by using ME-49 and RH strains. The results suggest low to moderate toxicity for both compounds. Thymol was more toxic in vivo and in vitro, having greater pathological repercussion than Estragole. The compounds were inactive for antiproliferative activity. Thymol showed better antioxidant activity, while Estragole stimulated nitric oxide production in macrophages. Both showed significant antiinflammatory activity. In non-congenital Tg infection, both compounds were active only against the ME49 strain. In congenital infection, Estragole (oral route) improved the newborn weight of infected mothers compared with untreated controls. Subcutaneous administration of the two compounds increased the weight of offspring born to infected mothers compared with untreated controls. We concluded that Estragole and Thymol exhibit important biological and anti-Toxoplasma activities. Further studies are needed to elucidate the mechanism of action of these compounds and other possible activities not investigated in the present study

Anti-leishmanial effects of purified compounds from aerial parts of Baccharis uncinella C. DC. (Asteraceae)

Species of Baccharis exhibit antibiotic, antiseptic, wound-healing, and anti-protozoal properties, and have been used in the traditional medicine of South America for the treatment of several diseases. In the present work, the fractionation of EtOH extract from aerial parts of Baccharis uncinella indicated that the isolated compounds caffeic acid and pectolinaringenin showed inhibitory activity against Leishmania (L.) amazonensis and Leishmania (V.) braziliensis promastigotes, respectively. Moreover, amastigote forms of both species were highly sensible to the fraction composed by oleanolic + ursolic acids and pectolinaringenin. Caffeic acid also inhibited amastigote forms of L. (L.) amazonensis, but this effect was weak in L. (V.) braziliensis amastigotes. The treatment of infected macrophages with these compounds did not alter the levels of nitrates, indicating a direct effect of the compounds on amastigote stages. The results presented herein suggest that the active components from B. uncinella can be important to the design of new drugs against American tegumentar leishmaniases.

Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Synthesis, characterization, X-ray structure and in vitro anti mycobacterial and antitumoral activities of Ru(II) phosphine/diimine complexes containing the "SpymMe(2)" ligand, SpymMe(2)=4,6-dimethyl-2-mercaptopyrimidine

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Synthesis and Anti-Mycobacterium tuberculosis Evaluation of Aza-Stilbene Derivatives

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Synergism between plant extract and antimicrobial drugs used on Staphylococcus aureus diseases

Searches for substances with antimicrobial activity are frequent, and medicinal plants have been considered interesting by some researchers since they are frequently used in popular medicine as remedies for many infectious diseases. The aim of this study was to verify the synergism between 13 antimicrobial drugs and 8 plant extracts - guaco (Mikania glomerata), guava (Psidium guajava), clove (Syzygium aromaticum), garlic (Allium sativum), lemongrass (Cymbopogon citratus), ginger (Zingiber officinale), carqueja (Baccharis trimera), and mint (Mentha piperita) - against Staphylococcus aureus strains, and for this purpose, the disk method was the antimicrobial susceptibility test performed. Petri dishes were prepared with or without dilution of plant extracts at sub-inhibitory concentrations in Mueller-Hinton Agar (MHA), and the inhibitory zones were recorded in millimeters. In vitro anti-Staphylococcus aureus activities of the extracts were confirmed, and synergism was verified for all the extracts; clove, guava, and lemongrass presented the highest synergism rate with antimicrobial drugs, while ginger and garlic showed limited synergistic capacity.

Anti-proliferative and cytotoxic activity of pentadactylin isolated from Leptodactylus labyrinthicus on melanoma cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Patents of drugs extracted from Brazilian medicinal plants

Background: Plants synthesise a vast repertoire of chemicals with various biological activities. Brazilian enormous botanical diversity facilitates the development of novel ethical drugs for the treatment of diseases in humans. Objective: To present therapeutic patent applications comprising Brazilian native plants published in the 2003 - 2008 period in light of legal aspects of patentability of biodiversity and public health concerns. Methods: Therapeutic patent applications related to Brazilian medicinal plants available at both the European Patent Office and the Brazilian National Institute of industrial Property databases were reviewed. Results/conclusion: Twenty-five patents are presented, most of which concern inflammatory, allergic, parasitic, infectious or digestive diseases, including extracts from Carapa guianensis, Copaifera genus, Cordia verbenacea, Erythrina mulungu, Physalis angulata and other pharmaceutical compositions with antileishmanial, antimalarial or trypanocidal activity. Brazilian research centres and universities are responsible for most of these inventions.

Oral drugs for hypertensive urgencies: systematic review and meta-analysis

CONTEXTO E OBJETIVO: Urgências hipertensivas são definidas como elevações graves na pressão arterial sem evidência de danos agudos ou progressivos a órgãos-alvo. A necessidade de tratamento é considerada urgente, mas permite um controle gradual, utilizando-se drogas orais ou sublinguais. Se o aumento na pressão arterial não está associado a risco de vida ou danos a órgãos alvo, o controle pressórico deve ser feito lentamente durante 24 horas. em relação às urgências hipertensivas, não é conhecida qual a classe de drogas anti-hipertensivas que promove os melhores resultados e há controvérsia em relação a quando e quais as drogas devem ser utilizadas nestas situações. O objetivo desta revisão foi avaliar a efetividade e a segurança de drogas orais para urgências hipertensivas. METODOS: Esta revisão sistemática da literatura foi desenvolvida no Centro Cochrane do Brasil, e na Disciplina de Medicina de Urgência e Medicina Baseada em Evidências da Universidade Federal de São Paulo (UNIFESP) - Escola Paulista de Medicina (Unifesp-EPM), de acordo com a metodologia da Colaboração Cochrane. RESULTADOS: Os 16 ensaios clínicos aleatórios selecionados incluíram 769 participantes e demonstraram um efeito superior dos inibidores da enzima conversora de angiotensina no tratamento da urgência hipertensiva, avaliada em 223 participantes. Os efeitos adversos mais frequentes para os bloqueadores de canal de cálcio foram cefaleia (35/206), rubor (17/172) e alterações do ritmo cardíaco (14/189); para os inibidores da enzima conversora de angiotensina, o efeito colateral mais frequente foi disgeusia (25/38). CONCLUSÕES: Há evidências importantes a favor do uso de inibidores da enzima conversora da angiotensina para o tratamento de urgências hipertensivas, quando comparados aos bloqueadores dos canais de cálcio, devido a maior efetividade e à menor frequência de efeitos adversos, como cefaléia e rubor facial.

Dissociation and electrooxidation of primaquine diphosphate as an approach to the study of anti-chagas prodrugs mechanism of action

This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH-dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized.This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown.This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs. (C) 2000 Elsevier B.V. S.A. All rights reserved.

Palladium(II) Complexes with Thiosemicarbazones. Syntheses, Characterization and Cytotoxicity against Breast Cancer Cells and Anti-Mycobacterium tuberculosis Activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)