iso-Kaurenoic acid from Wedelia paludosa D.C.

A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.

Uma recente reinvestigação das partes aéreas de Wedelia paludosa D.C. é descrita e relata, pela primeira vez, o isolamento do ácido iso-caurenóico desta espécie.

Plant-derived antimalarial agents: new leads and efficient phythomedicines: part 1: Alkaloids

Malaria remains one of the most serious world health problem and the major cause of mortality and morbidity in the endemic regions. Brazil is among the 30 high-burden countries and most of the cases occur in the Legal Amazonian Region. New chemotherapeutical agents are needed for the treatment of malaria. Many plant species are used in traditional medicines of malarious countries and a relatively few number of these have been investigated for evaluation of their antimalarial effect. Still lower is the number of those that have had the active natural compounds isolated and the toxicity determined. This area is, then, of great research interest. discovery project of antimalarial natural products from plants traditionally used to treat malaria must include in vitro and in vivo assays as well as bioguided isolation of active compounds. The final products would be antimalarial chemical entities, potential new drugs or templates for new drugs development, and/or standardized antimalarial extracts which are required for pre-clinical and clinical studies when the aim is the development of effective and safe phythomedicines. This review discusses these two approaches, presents briefly the screening methodologies for evaluation of antimalarial activity and focuses the activity of alkaloids belonging to different structural classes as well as its importance as new antimalarial drugs or leads and chemical markers for phytomedicines.

A malária ainda é um dos mais sérios problemas de saúde pública e a principal causa de mortalidade e morbidade nas regiões endêmicas. O Brasil está entre os 30 países com maior incidência de malária e a maior parte dos casos ocorre na Amazônia Legal. Novos agentes terapêuticos são necessários para o tratamento da malária. Muitas espécies vegetais são utilizadas na medicina tradicional de vários países endêmicos mas é relativamente reduzido o número daquelas que já foram investigadas quanto à sua atividade antimalárica. Menor ainda é o número de espécies das quais foram isoladas substâncias ativas e tiveram sua toxidade determinada. Esta área de pesquisa é, portanto, de alta relevância. Um projeto de descoberta de produtos naturais antimaláricos a partir de plantas de uso tradicional deve incluir ensaios in vitro e in vivo bem como o isolamento biomonitorado de substâncias ativas. Os produtos finais serão substâncias naturais antimaláricas, potenciais fármacos ou protótipos para o desenvolvimento de novos fármacos, e/ou extratos padronizados, com atividade antimalárica, os quais são necessários para estudos pré-clínicos e clínicos quando o objetivo é o desenvolvimento de fitoterápicos (fitomedicamentos) eficazes e seguros. A presente revisão discute estas duas abordagens, apresenta resumidamente as metodologias de bioensaios para avaliação de atividade antimalárica e focaliza a atividade de alcalóides pertencentes a diferentes classes estruturais bem como sua importância como fármacos ou protótipos e como marcadores químicos de fitoterápicos.

Cytotoxicity of Wedelia paludosa D.C. extracts and constituents / Citotoxidade de extratos e constituintes de Wedelia paludosa D.C

Wedelia paludosa D.C. (Asteraceae) is an ornamental species occurring in many regions of Brazil. Aiming to find new cytotoxic compounds, the hydromethanol extract of W. paludosa (HME), as well as the dichloromethane (DF) and water (WF) fractions resulting from its partition, were submitted to the brine shrimp lethality bioassay (BSLB) in order to evaluate their cytotoxicity. Dichloromethane fraction (DF) was shown to be the most cytotoxic fraction (LC50 = 140.6 μg/mL), and its analysis by reversed phase high performance liquid chromatography (RP-HPLC) revealed ent-kaurenoic (1, 6.22 ± 0.23 percent) and grandiflorenic (2, 3.22 ± 0.31 percent) acids as important constituents. HME (LC50 = 980 μg/mL), DF (LC50 = 140.6 μg/mL), 1 (LC50 = 15.9 μg/mL) and 2 (LC50 = 29.8 μg/mL) were found to be cytotoxic, while the water fraction (WF, LC50 >> 1000 μg/mL) was inactive. As conclusion, the cytotoxicity observed for HME and DF is mainly due to the presence of 1 and 2 in their constitution.

Wedelia paludosa D.C. (Asteraceae) é uma planta ornamental facilmente encontrada em várias regiões do Brasil, principalmente nos estados de Santa Catarina, São Paulo, Minas Gerais, Bahia e Pernambuco. Objetivando descobrir novas substâncias citotóxicas a partir desta espécie, o extrato hidrometanólico de W. paludosa (HME) e as frações diclorometânica (FD) e aquosa (FA) resultantes de sua partição em CH2Cl2-H2O foram avaliados utilizando-se o bioensaio em Artemia salina. A fração diclorometânica (FD) apresentou a maior atividade citotóxica (CL50 = 140,6 μg/mL), e sua análise por cromatografia líquida de alta eficiência empregando-se fase reversa (FR-CLAE) revelou os ácidos caurenóico (1, 6,22 ± 0,23 por cento) e grandiflorênico (2, 3,22 ± 0,31 por cento) como constituintes majoritários. As amostras HME (CL50 = 980 μg/mL), FD (CLC50 = 140,6 μg/mL), 1 (CL50 = 15,9 μg/mL) e 2 (CL50 = 29,8 μg/mL) foram citotóxicas contra A. salina, enquanto que a fração aquosa (FA, CL50 >> 1000 μg/mL) mostrou-se inativa. Conclui-se que a citotoxidade observada para HME e FD pode ser atribuída à presença dos ácidos caurenóico (1) e grandiflorênico (2) nestes extratos.

Preparation and activity of diterpenoids against trypomastigotes of Trypanosoma cruzi

A systematic investigation on the trypanocidal effect of several natural products isolated from Brazilian plant species has been carried out. In this paper we report on the results obtained from the screening of 26 diterpenes from natural sources or of synthetic/microbial transformations origin (mainly derivatives of kaurenoic acid) against trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas'disease. In the in vitro assays, kaurenoic acid, kaurenol, acutifloric acid and stemodin showed a complete elimination of parasites from the blood. Therefore, such diterpenoids can be considered as starting materials for molecular modification in the search for lead compounds for clearance of infected blood to be used in transfusions. Blood previously treated with active compounds was submitted to an infectivity test. Samples proceeded from treatment with kaurenol and kaurenoic acid showed to be completly clean from T. cruzi as no infection was observed in mice inoculated with contaminated blood treated by these compounds.

Screening of Asteraceae (Compositae) plant extracts for larvicidal activity against Aedes fluviatilis (Diptera: Culicidae)

Ethanol extracts of 83 plants species belonging to the Asteraceae (Compositae) family, collectes in the State of Minas Gerais, Brazil, were tested for larvicidal activity against the mosquito Aedes fluviatilis - Diptera: Culicidae). The extract from Tagetes minuta was the most active with LC90 of 1.5 mg/l and LC50 of 1.0 mg/l. This plant been the object of several studies by other groups and its active components have already been identified as thiophene derivates, a class of compounds present in many Asteraceae species. The extract of Eclipta paniculata was also significantly active, with a LC90 of 17.2 mg/l and LC50 of 3.3 mg/l and no previous studies on its larvicidal activity or chemical composition could be found in the literature. Extracts of Achryrocline satureoides, Gnaphalium spicatum, Senecio brasiliensis, Trixis vauthieri, Tagetes patula and Vernonia ammophila were less active, killing more than 50 per cent of the larvae only at the higher dose tested (100 mg/l)